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Sample records for alzheimers disease brain

  1. Brain Imaging in Alzheimer Disease

    Science.gov (United States)

    Johnson, Keith A.; Fox, Nick C.; Sperling, Reisa A.; Klunk, William E.

    2012-01-01

    Imaging has played a variety of roles in the study of Alzheimer disease (AD) over the past four decades. Initially, computed tomography (CT) and then magnetic resonance imaging (MRI) were used diagnostically to rule out other causes of dementia. More recently, a variety of imaging modalities including structural and functional MRI and positron emission tomography (PET) studies of cerebral metabolism with fluoro-deoxy-d-glucose (FDG) and amyloid tracers such as Pittsburgh Compound-B (PiB) have shown characteristic changes in the brains of patients with AD, and in prodromal and even presymptomatic states that can help rule-in the AD pathophysiological process. No one imaging modality can serve all purposes as each have unique strengths and weaknesses. These modalities and their particular utilities are discussed in this article. The challenge for the future will be to combine imaging biomarkers to most efficiently facilitate diagnosis, disease staging, and, most importantly, development of effective disease-modifying therapies. PMID:22474610

  2. Alzheimer disease

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    Senile dementia - Alzheimer type (SDAT); SDAT; Dementia - Alzheimer ... The exact cause of Alzheimer disease is not known. Research shows that certain changes in the brain lead to Alzheimer disease. You are more likely ...

  3. Robust gene dysregulation in Alzheimer's disease brains.

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    Feng, Xuemei; Bai, Zhouxian; Wang, Jiajia; Xie, Bin; Sun, Jiya; Han, Guangchun; Song, Fuhai; Crack, Peter J; Duan, Yong; Lei, Hongxing

    2014-01-01

    The brain transcriptome of Alzheimer's disease (AD) reflects the prevailing disease mechanism at the gene expression level. However, thousands of genes have been reported to be dysregulated in AD brains in existing studies, and the consistency or discrepancy among these studies has not been thoroughly examined. Toward this end, we conducted a comprehensive survey of the brain transcriptome datasets for AD and other neurological diseases. We first demonstrated that the frequency of observed dysregulation in AD was highly correlated with the reproducibility of the dysregulation. Based on this observation, we selected 100 genes with the highest frequency of dysregulation to illustrate the core perturbation in AD brains. The dysregulation of these genes was validated in several independent datasets for AD. We further identified 12 genes with strong correlation of gene expression with disease progression. The relevance of these genes to disease progression was also validated in an independent dataset. Interestingly, we found a transcriptional "cushion" for these 100 genes in the less vulnerable visual cortex region, which may be a critical component of the protection mechanism for less vulnerable brain regions. To facilitate the research in this field, we have provided the expression information of ~8000 relevant genes on a publicly accessible web server AlzBIG (http://alz.big.ac.cn).

  4. Aluminium in brain tissue in familial Alzheimer's disease.

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    Mirza, Ambreen; King, Andrew; Troakes, Claire; Exley, Christopher

    2017-03-01

    The genetic predispositions which describe a diagnosis of familial Alzheimer's disease can be considered as cornerstones of the amyloid cascade hypothesis. Essentially they place the expression and metabolism of the amyloid precursor protein as the main tenet of disease aetiology. However, we do not know the cause of Alzheimer's disease and environmental factors may yet be shown to contribute towards its onset and progression. One such environmental factor is human exposure to aluminium and aluminium has been shown to be present in brain tissue in sporadic Alzheimer's disease. We have made the first ever measurements of aluminium in brain tissue from 12 donors diagnosed with familial Alzheimer's disease. The concentrations of aluminium were extremely high, for example, there were values in excess of 10μg/g tissue dry wt. in 5 of the 12 individuals. Overall, the concentrations were higher than all previous measurements of brain aluminium except cases of known aluminium-induced encephalopathy. We have supported our quantitative analyses using a novel method of aluminium-selective fluorescence microscopy to visualise aluminium in all lobes of every brain investigated. The unique quantitative data and the stunning images of aluminium in familial Alzheimer's disease brain tissue raise the spectre of aluminium's role in this devastating disease. Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.

  5. Alzheimer's Disease

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    Alzheimer's disease (AD) is the most common form of dementia among older people. Dementia is a brain disorder that ... higher if a family member has had the disease. No treatment can stop the disease. However, some ...

  6. Brain aging, Alzheimer's disease, and mitochondria

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    Swerdlow, Russell H.

    2011-01-01

    The relationship between brain aging and Alzheimer’s disease (AD) is contentious. One view holds AD results when brain aging surpasses a threshold. The other view postulates AD is not a consequence of brain aging. This review discusses this conundrum from the perspective of different investigative lines that have tried to address it, as well as from the perspective of the mitochondrion, an organelle that appears to play a role in both AD and brain aging. Specific issues addressed include the question of whether AD and brain aging should be conceptually lumped or split, the extent to which AD and brain aging potentially share common molecular mechanisms, whether beta amyloid should be primarily considered a marker of AD or simply brain aging, and the definition of AD itself. PMID:21920438

  7. The rationale for deep brain stimulation in Alzheimer's disease.

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    Mirzadeh, Zaman; Bari, Ausaf; Lozano, Andres M

    2016-07-01

    Alzheimer's disease is a major worldwide health problem with no effective therapy. Deep brain stimulation (DBS) has emerged as a useful therapy for certain movement disorders and is increasingly being investigated for treatment of other neural circuit disorders. Here we review the rationale for investigating DBS as a therapy for Alzheimer's disease. Phase I clinical trials of DBS targeting memory circuits in Alzheimer's disease patients have shown promising results in clinical assessments of cognitive function, neurophysiological tests of cortical glucose metabolism, and neuroanatomical volumetric measurements showing reduced rates of atrophy. These findings have been supported by animal studies, where electrical stimulation of multiple nodes within the memory circuit have shown neuroplasticity through stimulation-enhanced hippocampal neurogenesis and improved performance in memory tasks. The precise mechanisms by which DBS may enhance memory and cognitive functions in Alzheimer's disease patients and the degree of its clinical efficacy continue to be examined in ongoing clinical trials.

  8. Influence of cerebrovascular disease on brain networks in prodromal and clinical Alzheimer's disease.

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    Chong, Joanna Su Xian; Liu, Siwei; Loke, Yng Miin; Hilal, Saima; Ikram, Mohammad Kamran; Xu, Xin; Tan, Boon Yeow; Venketasubramanian, Narayanaswamy; Chen, Christopher Li-Hsian; Zhou, Juan

    2017-11-01

    Network-sensitive neuroimaging methods have been used to characterize large-scale brain network degeneration in Alzheimer's disease and its prodrome. However, few studies have investigated the combined effect of Alzheimer's disease and cerebrovascular disease on brain network degeneration. Our study sought to examine the intrinsic functional connectivity and structural covariance network changes in 235 prodromal and clinical Alzheimer's disease patients with and without cerebrovascular disease. We focused particularly on two higher-order cognitive networks-the default mode network and the executive control network. We found divergent functional connectivity and structural covariance patterns in Alzheimer's disease patients with and without cerebrovascular disease. Alzheimer's disease patients without cerebrovascular disease, but not Alzheimer's disease patients with cerebrovascular disease, showed reductions in posterior default mode network functional connectivity. By comparison, while both groups exhibited parietal reductions in executive control network functional connectivity, only Alzheimer's disease patients with cerebrovascular disease showed increases in frontal executive control network connectivity. Importantly, these distinct executive control network changes were recapitulated in prodromal Alzheimer's disease patients with and without cerebrovascular disease. Across Alzheimer's disease patients with and without cerebrovascular disease, higher default mode network functional connectivity z-scores correlated with greater hippocampal volumes while higher executive control network functional connectivity z-scores correlated with greater white matter changes. In parallel, only Alzheimer's disease patients without cerebrovascular disease showed increased default mode network structural covariance, while only Alzheimer's disease patients with cerebrovascular disease showed increased executive control network structural covariance compared to controls. Our

  9. Blood-Brain Glucose Transfer in Alzheimer's disease

    DEFF Research Database (Denmark)

    Gejl, Michael; Brock, Birgitte; Egefjord, Lærke

    2017-01-01

    There are fewer than normal glucose transporters at the blood-brain barrier (BBB) in Alzheimer's disease (AD). When reduced expression of transporters aggravates the symptoms of AD, the transporters become a potential target of therapy. The incretin hormone GLP-1 prevents the decline of cerebral...

  10. Energy metabolism and inflammation in brain aging and Alzheimer's disease.

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    Yin, Fei; Sancheti, Harsh; Patil, Ishan; Cadenas, Enrique

    2016-11-01

    The high energy demand of the brain renders it sensitive to changes in energy fuel supply and mitochondrial function. Deficits in glucose availability and mitochondrial function are well-known hallmarks of brain aging and are particularly accentuated in neurodegenerative disorders such as Alzheimer's disease. As important cellular sources of H 2 O 2 , mitochondrial dysfunction is usually associated with altered redox status. Bioenergetic deficits and chronic oxidative stress are both major contributors to cognitive decline associated with brain aging and Alzheimer's disease. Neuroinflammatory changes, including microglial activation and production of inflammatory cytokines, are observed in neurodegenerative diseases and normal aging. The bioenergetic hypothesis advocates for sequential events from metabolic deficits to propagation of neuronal dysfunction, to aging, and to neurodegeneration, while the inflammatory hypothesis supports microglia activation as the driving force for neuroinflammation. Nevertheless, growing evidence suggests that these diverse mechanisms have redox dysregulation as a common denominator and connector. An independent view of the mechanisms underlying brain aging and neurodegeneration is being replaced by one that entails multiple mechanisms coordinating and interacting with each other. This review focuses on the alterations in energy metabolism and inflammatory responses and their connection via redox regulation in normal brain aging and Alzheimer's disease. Interaction of these systems is reviewed based on basic research and clinical studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. CARS microscopy of Alzheimer's diseased brain tissue

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    Enejder, Annika; Kiskis, Juris; Fink, Helen; Nyberg, Lena; Thyr, Jakob; Li, Jia-Yi

    2014-02-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder currently without cure, characterized by the presence of extracellular plaques surrounded by dystrophic neurites. In an effort to understand the underlying mechanisms, biochemical analysis (protein immunoblot) of plaque extracts reveals that they consist of amyloid-beta (Aβ) peptides assembled as oligomers, protofibrils and aggregates. Their spatial distribution has been confirmed by Thioflavin-S or immuno-staining with fluorescence microscopy. However, it is increasingly understood that the protein aggregation is only one of several mechanism that causes neuronal dysfunction and death. This raises the need for a more complete biochemical analysis. In this study, we have complemented 2-photon fluorescence microscopy of Thioflavin-S and Aβ immuno-stained human AD plaques with CARS microscopy. We show that the chemical build-up of AD plaques is more complex and that Aβ staining does not provide the complete picture of the spatial distribution or the molecular composition of AD plaques. CARS images provide important complementary information to that obtained by fluorescence microscopy, motivating a broader introduction of CARS microscopy in the AD research field.

  12. Lipidomics of human brain aging and Alzheimer's disease pathology.

    Science.gov (United States)

    Naudí, Alba; Cabré, Rosanna; Jové, Mariona; Ayala, Victoria; Gonzalo, Hugo; Portero-Otín, Manuel; Ferrer, Isidre; Pamplona, Reinald

    2015-01-01

    Lipids stimulated and favored the evolution of the brain. Adult human brain contains a large amount of lipids, and the largest diversity of lipid classes and lipid molecular species. Lipidomics is defined as "the full characterization of lipid molecular species and of their biological roles with respect to expression of proteins involved in lipid metabolism and function, including gene regulation." Therefore, the study of brain lipidomics can help to unravel the diversity and to disclose the specificity of these lipid traits and its alterations in neural (neurons and glial) cells, groups of neural cells, brain, and fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of human brain aging and Alzheimer disease. This review will discuss the lipid composition of the adult human brain. We first consider a brief approach to lipid definition, classification, and tools for analysis from the new point of view that has emerged with lipidomics, and then turn to the lipid profiles in human brain and how lipids affect brain function. Finally, we focus on the current status of lipidomics findings in human brain aging and Alzheimer's disease pathology. Neurolipidomics will increase knowledge about physiological and pathological functions of brain cells and will place the concept of selective neuronal vulnerability in a lipid context. © 2015 Elsevier Inc. All rights reserved.

  13. Deregulation of brain insulin signaling in Alzheimer's disease.

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    Chen, Yanxing; Deng, Yanqiu; Zhang, Baorong; Gong, Cheng-Xin

    2014-04-01

    Contrary to the previous belief that insulin does not act in the brain, studies in the last three decades have demonstrated important roles of insulin and insulin signal transduction in various functions of the central nervous system. Deregulated brain insulin signaling and its role in molecular pathogenesis have recently been reported in Alzheimer's disease (AD). In this article, we review the roles of brain insulin signaling in memory and cognition, the metabolism of amyloid β precursor protein, and tau phosphorylation. We further discuss deficiencies of brain insulin signaling and glucose metabolism, their roles in the development of AD, and recent studies that target the brain insulin signaling pathway for the treatment of AD. It is clear now that deregulation of brain insulin signaling plays an important role in the development of sporadic AD. The brain insulin signaling pathway also offers a promising therapeutic target for treating AD and probably other neurodegenerative disorders.

  14. Blood-Brain Glucose Transfer in Alzheimer's disease

    DEFF Research Database (Denmark)

    Gejl, Michael; Brock, Birgitte; Egefjord, Lærke

    2017-01-01

    There are fewer than normal glucose transporters at the blood-brain barrier (BBB) in Alzheimer's disease (AD). When reduced expression of transporters aggravates the symptoms of AD, the transporters become a potential target of therapy. The incretin hormone GLP-1 prevents the decline of cerebral...... metabolic rate for glucose (CMRglc) in AD, and GLP-1 may serve to raise transporter numbers. We hypothesized that the GLP-1 analog liraglutide would prevent the decline of CMRglc in AD by raising blood-brain glucose transfer, depending on the duration of disease. We randomized 38 patients with AD...

  15. Alzheimer's disease.

    Science.gov (United States)

    Scheltens, Philip; Blennow, Kaj; Breteler, Monique M B; de Strooper, Bart; Frisoni, Giovanni B; Salloway, Stephen; Van der Flier, Wiesje Maria

    2016-07-30

    Although the prevalence of dementia continues to increase worldwide, incidence in the western world might have decreased as a result of better vascular care and improved brain health. Alzheimer's disease, the most prevalent cause of dementia, is still defined by the combined presence of amyloid and tau, but researchers are gradually moving away from the simple assumption of linear causality as proposed in the original amyloid hypothesis. Age-related, protective, and disease-promoting factors probably interact with the core mechanisms of the disease. Amyloid β42, and tau proteins are established core cerebrospinal biomarkers; novel candidate biomarkers include amyloid β oligomers and synaptic markers. MRI and fluorodeoxyglucose PET are established imaging techniques for diagnosis of Alzheimer's disease. Amyloid PET is gaining traction in the clinical arena, but validity and cost-effectiveness remain to be established. Tau PET might offer new insights and be of great help in differential diagnosis and selection of patients for trials. In the search for understanding the disease mechanism and keys to treatment, research is moving increasingly into the earliest phase of disease. Preclinical Alzheimer's disease is defined as biomarker evidence of Alzheimer's pathological changes in cognitively healthy individuals. Patients with subjective cognitive decline have been identified as a useful population in whom to look for preclinical Alzheimer's disease. Moderately positive results for interventions targeting several lifestyle factors in non-demented elderly patients and moderately positive interim results for lowering amyloid in pre-dementia Alzheimer's disease suggest that, ultimately, there will be a future in which specific anti-Alzheimer's therapy will be combined with lifestyle interventions targeting general brain health to jointly combat the disease. In this Seminar, we discuss the main developments in Alzheimer's research. Copyright © 2016 Elsevier Ltd. All

  16. Regional brain stiffness changes across the Alzheimer's disease spectrum

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    Matthew C. Murphy

    2016-01-01

    Full Text Available Magnetic resonance elastography (MRE is an MRI-based technique to noninvasively measure tissue stiffness. Currently well established for clinical use in the liver, MRE is increasingly being investigated to measure brain stiffness as a novel biomarker of a variety of neurological diseases. The purpose of this work was to apply a recently developed MRE pipeline to measure regional brain stiffness changes in human subjects across the Alzheimer's disease (AD spectrum, and to gain insights into the biological processes underlying those stiffness changes by correlating stiffness with existing biomarkers of AD. The results indicate that stiffness changes occur mostly in the frontal, parietal and temporal lobes, in accordance with the known topography of AD pathology. Furthermore, stiffness in those areas correlates with existing imaging biomarkers of AD including hippocampal volumes and amyloid PET. Additional analysis revealed preliminary but significant evidence that the relationship between brain stiffness and AD severity is nonlinear and non-monotonic. Given that similar relationships have been observed in functional MRI experiments, we used task-free fMRI data to test the hypothesis that brain stiffness was sensitive to structural changes associated with altered functional connectivity. The analysis revealed that brain stiffness is significantly and positively correlated with default mode network connectivity. Therefore, brain stiffness as measured by MRE has potential to provide new and essential insights into the temporal dynamics of AD, as well as the relationship between functional and structural plasticity as it relates to AD pathophysiology.

  17. Genetics Home Reference: Alzheimer disease

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    ... Email Facebook Twitter Home Health Conditions Alzheimer disease Alzheimer disease Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Alzheimer disease is a degenerative disease of the brain ...

  18. Deficient brain insulin signalling pathway in Alzheimer's disease and diabetes.

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    Liu, Ying; Liu, Fei; Grundke-Iqbal, Inge; Iqbal, Khalid; Gong, Cheng-Xin

    2011-09-01

    Brain glucose metabolism is impaired in Alzheimer's disease (AD), the most common form of dementia. Type 2 diabetes mellitus (T2DM) is reported to increase the risk for dementia, including AD, but the underlying mechanism is not understood. Here, we investigated the brain insulin-PI3K-AKT signalling pathway in the autopsied frontal cortices from nine AD, 10 T2DM, eight T2DM-AD and seven control cases. We found decreases in the levels and activities of several components of the insulin-PI3K-AKT signalling pathway in AD and T2DM cases. The deficiency of insulin-PI3K-AKT signalling was more severe in individuals with both T2DM and AD (T2DM-AD). This decrease in insulin-PI3K-AKT signalling could lead to activation of glycogen synthase kinase-3β, the major tau kinase. The levels and the activation of the insulin-PI3K-AKT signalling components correlated negatively with the level of tau phosphorylation and positively with protein O-GlcNAcylation, suggesting that impaired insulin-PI3K-AKT signalling might contribute to neurodegeneration in AD through down-regulation of O-GlcNAcylation and the consequent promotion of abnormal tau hyperphosphorylation and neurodegeneration. The decrease in brain insulin-PI3K-AKT signalling also correlated with the activation of calpain I in the brain, suggesting that the decrease might be caused by calpain over-activation. Our findings provide novel insight into the molecular mechanism by which type 2 diabetes mellitus increases the risk for developing cognitive impairment and dementia in Alzheimer's disease. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  19. Microprobe PIXE analysis and EDX analysis on the brain of patients with Alzheimer's disease

    International Nuclear Information System (INIS)

    Yumoto, S.; Horino, Y.; Mokuno, Y.; Fujii, K.; Kakimi, S.; Mizutani, T.; Matsushima, H.; Ishikawa, A.

    1996-01-01

    To investigate the cause of Alzheimer's disease (senile dementia of Alzheimer's disease type), we examined aluminium (Al) in the brain (hippocampus) of patients with Alzheimer's disease using heavy ion (5 MeV Si 3+ ) microprobe particle-induced X-ray emission (PIXE) analysis. Heavy ion microprobes (3 MeV Si 2+ ) have several times higher sensitivity for Al detection than 2 MeV proton microprobes. We also examined Al in the brain of these patients by energy dispersive X-ray spectroscopy (EDX). (1) Al was detected in the cell nuclei isolated from the brain of patients with Alzheimer's disease using 5 MeV Si 3+ microprobe PIXE analysis, and EDX analysis. (2) EDX analysis demonstrated high levels of Al in the nucleolus of nerve cells in frozen sections prepared from the brain of these patients. Our results support the theory that Alzheimer's disease is caused by accumulation of Al in the nuclei of brain cells. (author)

  20. Altered subcellular localization of ornithine decarboxylase in Alzheimer's disease brain

    International Nuclear Information System (INIS)

    Nilsson, Tatjana; Bogdanovic, Nenad; Volkman, Inga; Winblad, Bengt; Folkesson, Ronnie; Benedikz, Eirikur

    2006-01-01

    The amyloid precursor protein can through ligand-mimicking induce expression of ornithine decarboxylase (ODC), the initial and rate-limiting enzyme in polyamine biosynthesis. We report here the regional distribution and cellular localization of ODC immunoreactivity in Alzheimer's disease (AD) brains. In frontal cortex and hippocampus of control cases, the most pronounced ODC immunoreactivity was found in the nucleus. In possible and definite AD the immunoreactivity had shifted to the cytoplasm. In cerebellum of control cases, ODC staining was found in a small portion of Purkinje cells, mostly in the nucleus. In AD, both possible and definite, the number of stained Purkinje cells increased significantly and immunoreactivity was shifted to the cytoplasm, even though it was still prominent in the nucleus. In conclusion, our study reveals an early shift of the ODC immunoreactivity in AD from the nuclear compartment towards the cytoplasm

  1. Alzheimer's disease gene signature says: beware of brain viral infections

    Directory of Open Access Journals (Sweden)

    Ianni Manuela

    2010-12-01

    Full Text Available Abstract Background Recent findings from a genome wide association investigation in a large cohort of patients with Alzheimer's disease (AD and non demented controls (CTR showed that a limited set of genes was in a strong association (p > l0-5 with the disease. Presentation of the hypothesis In this report we suggest that the polymorphism association in 8 of these genes is consistent with a non conventional interpretation of AD etiology. Nectin-2 (NC-2, apolipoprotein E (APOE, glycoprotein carcinoembryonic antigen related cell adhesion molecule- 16 (CEACAM-16, B-cell lymphoma-3 (Bcl-3, translocase of outer mitochondrial membrane 40 homolog (T0MM-40, complement receptor-1 (CR-l, APOJ or clusterin and C-type lectin domain A family-16 member (CLEC-16A result in a genetic signature that might affect individual brain susceptibility to infection by herpes virus family during aging, leading to neuronal loss, inflammation and amyloid deposition. Implications of the hypothesis We hypothesized that such genetic trait may predispose to AD via complex and diverse mechanisms each contributing to an increase of individual susceptibility to brain viral infections

  2. Alzheimer's disease pattern of brain atrophy predicts cognitive decline in Parkinson's disease

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    Dietz, Nicole; Duda, John E.; Wolk, David A.; Doshi, Jimit; Xie, Sharon X.; Davatzikos, Christos; Clark, Christopher M.; Siderowf, Andrew

    2012-01-01

    Research suggests overlap in brain regions undergoing neurodegeneration in Parkinson's and Alzheimer's disease. To assess the clinical significance of this, we applied a validated Alzheimer's disease-spatial pattern of brain atrophy to patients with Parkinson's disease with a range of cognitive abilities to determine its association with cognitive performance and decline. At baseline, 84 subjects received structural magnetic resonance imaging brain scans and completed the Dementia Rating Scale-2, and new robust and expanded Dementia Rating Scale-2 norms were applied to cognitively classify participants. Fifty-nine non-demented subjects were assessed annually with the Dementia Rating Scale-2 for two additional years. Magnetic resonance imaging scans were quantified using both a region of interest approach and voxel-based morphometry analysis, and a method for quantifying the presence of an Alzheimer's disease spatial pattern of brain atrophy was applied to each scan. In multivariate models, higher Alzheimer's disease pattern of atrophy score was associated with worse global cognitive performance (β = −0.31, P = 0.007), including in non-demented patients (β = −0.28, P = 0.05). In linear mixed model analyses, higher baseline Alzheimer's disease pattern of atrophy score predicted long-term global cognitive decline in non-demented patients [F(1, 110) = 9.72, P = 0.002], remarkably even in those with normal cognition at baseline [F(1, 80) = 4.71, P = 0.03]. In contrast, in cross-sectional and longitudinal analyses there was no association between region of interest brain volumes and cognitive performance in patients with Parkinson's disease with normal cognition. These findings support involvement of the hippocampus and parietal–temporal cortex with cognitive impairment and long-term decline in Parkinson's disease. In addition, an Alzheimer's disease pattern of brain atrophy may be a preclinical biomarker of cognitive decline

  3. Altered subcellular localization of ornithine decarboxylase in Alzheimer's disease brain

    DEFF Research Database (Denmark)

    Nilsson, Tatjana; Bogdanovic, Nenad; Volkman, Inga

    2006-01-01

    The amyloid precursor protein can through ligand-mimicking induce expression of ornithine decarboxylase (ODC), the initial and rate-limiting enzyme in polyamine biosynthesis. We report here the regional distribution and cellular localization of ODC immunoreactivity in Alzheimer's disease (AD...

  4. A derangement of the brain wound healing process may cause some cases of Alzheimer's disease.

    Science.gov (United States)

    Lehrer, Steven; Rheinstein, Peter H

    2016-08-01

    A derangement of brain wound healing may cause some cases of Alzheimer's disease. Wound healing, a highly complex process, has four stages: hemostasis, inflammation, repair, and remodeling. Hemostasis and the initial phases of inflammation in brain tissue are typical of all vascularized tissue, such as skin. However, distinct differences arise in brain tissue during the later stages of inflammation, repair, and remodeling, and closely parallel the changes of Alzheimer's disease. Our hypothesis -- Alzheimer's disease is brain wound healing gone awry at least in some cases -- could be tested by measuring progression with biomarkers for the four stages of wound healing in humans or appropriate animal models. Autopsy studies might be done. Chronic traumatic encephalopathy might also result from the brain wound healing process.

  5. Deep brain stimulation for people with Alzheimer's disease: Anticipating potential effects on the tripartite self.

    Science.gov (United States)

    Viaña, John Noel M; Gilbert, Frederic

    2018-01-01

    Memory dysfunction and cognitive impairments due to Alzheimer's disease can affect the selfhood and identity of afflicted individuals, causing distress to both people with Alzheimer's disease and their caregivers. Recently, a number of case studies and clinical trials have been conducted to determine the potential of deep brain stimulation as a therapeutic modality for people with Alzheimer's disease. Some of these studies have shown that deep brain stimulation could induce flashbacks and stabilize or even improve memory. However, deep brain stimulation itself has also been attributed as a potential threat to identity and selfhood, especially when procedure-related adverse events arise. We anticipate potential effects of deep brain stimulation for people with Alzheimer's disease on selfhood, reconciling information from medical reports, psychological, and sociological investigations on the impacts of deep brain stimulation or Alzheimer's disease on selfhood. A tripartite model of the self that extends the scope of Rom Harré's and Steve Sabat's social constructionist framework was used. In this model, potential effects of deep brain stimulation for Alzheimer's disease on Self 1 or singularity through use of first-person indexicals, and gestures of self-reference, attribution, and recognition; Self 2 or past and present attributes, knowledge of these characteristics, and continuity of narrative identity; and Self 3 or the relational and social self are explored. The ethical implications of potential effects of deep brain stimulation for Alzheimer's disease on the tripartite self are then highlighted, focusing on adapting informed consent procedures and care provided throughout the trial to account for both positive and negative plausible effects on Self 1, Self 2, and Self 3.

  6. How Alzheimer's Changes the Brain

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    Full Text Available ... free Find out why Close How Alzheimer's Changes the Brain National Institute On Aging Loading... Unsubscribe from National ... Health Journey 169,151 views 2:20 Inside the Brain: Unraveling the Mystery of Alzheimer's Disease - Duration: 4: ...

  7. Data set of interactomes and metabolic pathways of proteins differentially expressed in brains with Alzheimer׳s disease

    Directory of Open Access Journals (Sweden)

    Benito Minjarez

    2016-06-01

    Full Text Available Alzheimer׳s disease is one of the main causes of dementia in the elderly and its frequency is on the rise worldwide. It is considered the result of complex interactions between genetic and environmental factors, being many of them unknown. Therefore, there is a dire necessity for the identification of novel molecular players for the understanding of this disease. In this data article we determined the protein expression profiles of whole protein extracts from cortex regions of brains from patients with Alzheimer׳s disease in comparison to a normal brain. We identified 721 iTRAQ-labeled polypeptides with more than 95% in confidence. We analyzed all proteins that changed in their expression level and located them in the KEGG metabolic pathways, as well as in the mitochondrial complexes of the electron transport chain and ATP synthase. In addition, we analyzed the over- and sub-expressed polypeptides through IPA software, specifically Core I and Biomarkers I modules. Data in this article is related to the research article “Identification of proteins that are differentially expressed in brains with Alzheimer’s disease using iTRAQ labeling and tandem mass spectrometry” (Minjarez et al., 2016 [1].

  8. Alzheimer's Disease: The Role of Microglia in Brain Homeostasis and Proteopathy

    Directory of Open Access Journals (Sweden)

    Kevin A. Clayton

    2017-12-01

    Full Text Available Brain aging is central to late-onset Alzheimer's disease (LOAD, although the mechanisms by which it occurs at protein or cellular levels are not fully understood. Alzheimer's disease is the most common proteopathy and is characterized by two unique pathologies: senile plaques and neurofibrillary tangles, the former accumulating earlier than the latter. Aging alters the proteostasis of amyloid-β peptides and microtubule-associated protein tau, which are regulated in both autonomous and non-autonomous manners. Microglia, the resident phagocytes of the central nervous system, play a major role in the non-autonomous clearance of protein aggregates. Their function is significantly altered by aging and neurodegeneration. This is genetically supported by the association of microglia-specific genes, TREM2 and CD33, and late onset Alzheimer's disease. Here, we propose that the functional characterization of microglia, and their contribution to proteopathy, will lead to a new therapeutic direction in Alzheimer's disease research.

  9. Elemental analysis of the frontal lobe of 'normal' brain tissue and that affected by Alzheimer's disease

    International Nuclear Information System (INIS)

    Stedman, J.D.; Spyrou, N.M.

    1997-01-01

    'Normal' brain tissue and brain tissue affected by Alzheimer's disease has been taken from the frontal lobe of both hemispheres and their elemental compositions in terms of major, minor and trace elements compared. Brain samples were obtained from the MRC Alzheimer's Disease Brain Bank, London. 25 samples were taken from 18 individuals (5 males and 13 females) of mean age 79.9 ± 7.3 years with pathologically confirmed Alzheimer's disease and 26 samples from 15 individuals (8 males and 7 females) of mean age 71.8 ± 13.0 years with no pathological sings of Alzheimer's disease ('normals'). The elemental concentration of the samples were determined by the techniques of Rutherford backscattering (RBS) analysis, particle induced X-ray emission (PIXE) analysis and instrumental neutron activation analysis (INAA). Na, Mg, Al, Cl, K, Sc, Fe, Zn, Se, Br, Rb and Cs were detected by INAA and significant differences in concentrations were found between concentrations in normal and Alzheimer tissue for the elements. Na, Cl, K, Se, Br and Rb, P, S, Cl, K, Ca, Fe, Zn and Cd were detected by PIXE analysis and significant differences found for the elements P, S, Cl, K and Ca. (author)

  10. Brain region's relative proximity as marker for Alzheimer's disease based on structural MRI

    DEFF Research Database (Denmark)

    Erleben, Lene Lillemark; Sørensen, Lauge Emil; Pai, Akshay Sadananda Uppinakudru

    2014-01-01

    BACKGROUND:Alzheimer's disease (AD) is a progressive, incurable neurodegenerative disease and the most common type of dementia. It cannot be prevented, cured or drastically slowed, even though AD research has increased in the past 5-10 years. Instead of focusing on the brain volume or on the single...

  11. White Matter Lipids as a Ketogenic Fuel Supply in Aging Female Brain: Implications for Alzheimer's Disease.

    Science.gov (United States)

    Klosinski, Lauren P; Yao, Jia; Yin, Fei; Fonteh, Alfred N; Harrington, Michael G; Christensen, Trace A; Trushina, Eugenia; Brinton, Roberta Diaz

    2015-12-01

    White matter degeneration is a pathological hallmark of neurodegenerative diseases including Alzheimer's. Age remains the greatest risk factor for Alzheimer's and the prevalence of age-related late onset Alzheimer's is greatest in females. We investigated mechanisms underlying white matter degeneration in an animal model consistent with the sex at greatest Alzheimer's risk. Results of these analyses demonstrated decline in mitochondrial respiration, increased mitochondrial hydrogen peroxide production and cytosolic-phospholipase-A2 sphingomyelinase pathway activation during female brain aging. Electron microscopic and lipidomic analyses confirmed myelin degeneration. An increase in fatty acids and mitochondrial fatty acid metabolism machinery was coincident with a rise in brain ketone bodies and decline in plasma ketone bodies. This mechanistic pathway and its chronologically phased activation, links mitochondrial dysfunction early in aging with later age development of white matter degeneration. The catabolism of myelin lipids to generate ketone bodies can be viewed as a systems level adaptive response to address brain fuel and energy demand. Elucidation of the initiating factors and the mechanistic pathway leading to white matter catabolism in the aging female brain provides potential therapeutic targets to prevent and treat demyelinating diseases such as Alzheimer's and multiple sclerosis. Targeting stages of disease and associated mechanisms will be critical.

  12. Tau, Amyloid Beta and Deep Brain Stimulation: Aiming to Restore Cognitive Deficit in Alzheimer's Disease.

    Science.gov (United States)

    Mondragón-Rodríguez, Siddhartha; Perry, George; Pena-Ortega, Fernando; Williams, Sylvain

    2017-01-01

    The last two decades have seen a great advance in the data that supports the two current hypotheses in Alzheimer`s disease field, the amyloid beta hypothesis and the tau hypothesis. Not surprisingly, Aβ and tau proteins are currently the major therapeutic research targets for AD treatment. Unfortunately, nothing but moderate success has emerged from such therapeutic approaches. With this in mind, we will discuss deep brain stimulation as a promising therapeutic strategy that aims to restore brain activity. Lastly, in the scope of cognitive deficit restoration, we will discuss the relevance of the limbic formation as a promising neuroanatomical target for deep brain stimulation. Immunohistochemistry for modified tau (phosphorylated at Ser199-202-Thr205 labelled by the antibody AT8) was performed on paraffin-embedded human brain sections providing a detailed characterization of NFT pathology. Abnormally phosphorylated tau protein is the key common marker in several brain diseases such as Alzheimer's disease, Parkinson`s disease, Pick Disease, Down syndrome and frontotemporal dementia and is capable of affecting synaptic events that are critical for memory formation. With this in mind, therapeutic strategies aiming to restore synaptic events could offer better outcomes. The humble success of current therapeutic strategies along with the lack of basic knowledge of the brain disease mechanisms calls for alternatives that benefit patients in the present moment. One of particular interest is the neurostimulation strategy that is already a well-established treatment for several movement disorders and when compared to current Alzheimer`s therapeutic strategies, deep brain stimulation does not directly interfere with the normal protein function, therefore increasing the probability of success.

  13. Neuroimaging of Alzheimer's disease

    International Nuclear Information System (INIS)

    Matsuda, Hiroshi

    2005-01-01

    Main purposes of neuroimaging in Alzheimer's disease have been moved from diagnosis of advanced Alzheimer's disease to diagnosis of very early Alzheimer's disease at a prodromal stage of mild cognitive impairment, prediction of conversion from mild cognitive impairment to Alzheimer's disease, and differential diagnosis from other diseases causing dementia. Structural MRI studies and functional studies using fluorodeoxyglucose (FDG)-PET and brain perfusion SPECT are widely used in diagnosis of Alzheimer's disease. Outstanding progress in diagnostic accuracy of these neuroimaging modalities has been obtained using statistical analysis on a voxel-by-voxel basis after spatial normalization of individual scans to a standardized brain-volume template instead of visual inspection or a conventional region of interest technique. In a very early stage of Alzheimer's disease, this statistical approach revealed gray matter loss in the entorhinal and hippocampal areas and hypometabolism or hypoperfusion in the posterior cingulate cortex. These two findings might be related in view of anatomical knowledge that the regions are linked through the circuit of Papez. This statistical approach also offers accurate evaluation of therapeutical effects on brain metabolism or perfusion. The latest development in functional imaging relates to the final pathological hallmark of Alzheimer's disease-amyloid plaques. Amyloid imaging might be an important surrogate marker for trials of disease-modifying agents. (author)

  14. Widespread Disruption of Functional Brain Organization in Early-Onset Alzheimer's Disease

    NARCIS (Netherlands)

    Adriaanse, S.M.; Binnewijzend, M.A.A.; Ossenkoppele, R.; Tijms, B.M.; van der Flier, W.M.; Koene, T.; Smits, L.L.; Wink, A.M.; Scheltens, P.; van Berckel, B.N.M.; Barkhof, F.

    2014-01-01

    Early-onset Alzheimer's disease (AD) patients present a different clinical profile than late-onset AD patients. This can be partially explained by cortical atrophy, although brain organization might provide more insight. The aim of this study was to examine functional connectivity in early-onset and

  15. How Alzheimer's Changes the Brain

    Medline Plus

    Full Text Available ... ideas to treat and prevent the disease. Category Science & Technology License Standard YouTube License Show more Show ... 5:15 Your Amazing Brain - Dementia Explained - Alzheimer's Research UK - Duration: 4:58. AlzheimersResearch UK 16,695 ...

  16. How Alzheimer's Changes the Brain

    Medline Plus

    Full Text Available ... ideas to treat and prevent the disease. Category Science & Technology License Standard YouTube License Show more Show ... 3:15 Your Amazing Brain - Dementia Explained - Alzheimer's Research UK - Duration: 4:58. AlzheimersResearch UK 16,411 ...

  17. How Alzheimer's Changes the Brain

    Medline Plus

    Full Text Available ... ideas to treat and prevent the disease. Category Science & Technology License Standard YouTube License Show more Show ... 9:57 Your Amazing Brain - Dementia Explained - Alzheimer's Research UK - Duration: 4:58. AlzheimersResearch UK 16,411 ...

  18. Neuroinflammation in Alzheimer's disease

    DEFF Research Database (Denmark)

    Heneka, Michael T; Carson, Monica J; Khoury, Joseph El

    2015-01-01

    Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia......, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded...... therapeutic or preventive strategies for Alzheimer's disease....

  19. The effect of aging on brain barriers and the consequences for Alzheimer's disease development.

    Science.gov (United States)

    Gorlé, Nina; Van Cauwenberghe, Caroline; Libert, Claude; Vandenbroucke, Roosmarijn E

    2016-08-01

    Life expectancy has increased in most developed countries, which has led to an increase in the proportion of elderly people in the world's population. However, this increase in life expectancy is not accompanied by a lengthening of the health span since aging is characterized with progressive deterioration in cellular and organ functions. The brain is particularly vulnerable to disease, and this is reflected in the onset of age-related neurodegenerative diseases such as Alzheimer's disease. Research shows that dysfunction of two barriers in the central nervous system (CNS), the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCSFB), plays an important role in the progression of these neurodegenerative diseases. The BBB is formed by the endothelial cells of the blood capillaries, whereas the BCSFB is formed by the epithelial cells of the choroid plexus (CP), both of which are affected during aging. Here, we give an overview of how these barriers undergo changes during aging and in Alzheimer's disease, thereby disturbing brain homeostasis. Studying these changes is needed in order to gain a better understanding of the mechanisms of aging at the brain barriers, which might lead to the development of new therapies to lengthen the health span (including mental health) and reduce the chances of developing Alzheimer's disease.

  20. Brain insulin signaling and Alzheimer's disease: current evidence and future directions.

    Science.gov (United States)

    Schiöth, Helgi B; Craft, Suzanne; Brooks, Samantha J; Frey, William H; Benedict, Christian

    2012-08-01

    Insulin receptors in the brain are found in high densities in the hippocampus, a region that is fundamentally involved in the acquisition, consolidation, and recollection of new information. Using the intranasal method, which effectively bypasses the blood-brain barrier to deliver and target insulin directly from the nose to the brain, a series of experiments involving healthy humans has shown that increased central nervous system (CNS) insulin action enhances learning and memory processes associated with the hippocampus. Since Alzheimer's disease (AD) is linked to CNS insulin resistance, decreased expression of insulin and insulin receptor genes and attenuated permeation of blood-borne insulin across the blood-brain barrier, impaired brain insulin signaling could partially account for the cognitive deficits associated with this disease. Considering that insulin mitigates hippocampal synapse vulnerability to amyloid beta and inhibits the phosphorylation of tau, pharmacological strategies bolstering brain insulin signaling, such as intranasal insulin, could have significant therapeutic potential to deter AD pathogenesis.

  1. Neuroprotective effect of the active components of three Chinese herbs on brain iron load in a mouse model of Alzheimer?s disease

    OpenAIRE

    DONG, XIAN-HUI; GAO, WEI-JUAN; KONG, WEI-NA; XIE, HONG-LIN; PENG, YAN; SHAO, TIE-MEI; YU, WEN-GUO; CHAI, XI-QING

    2015-01-01

    Alzheimer?s disease (AD) is a neurodegenerative brain disorder and the most common cause of dementia. New treatments for AD are required due to its increasing prevalence in aging populations. The present study evaluated the effects of the active components of Epimedium, Astragalus and Radix Puerariae on learning and memory impairment, ?-amyloid (A?) reduction and brain iron load in an APPswe/PS1?E9 transgenic mouse model of AD. Increasing evidence indicates that a disturbance of normal iron h...

  2. The Effect of Souvenaid on Functional Brain Network Organisation in Patients with Mild Alzheimer's Disease: A Randomised Controlled Study

    NARCIS (Netherlands)

    de Waal, H.; Stam, C.J.; Lansbergen, M.M.; Wieggers, R.L.; Kamphuis, P.J.G.H.; Scheltens, P.; Maestu, F.; van Straaten, E.C.W.

    2014-01-01

    Background: Synaptic loss is a major hallmark of Alzheimer's disease (AD). Disturbed organisation of large-scale functional brain networks in AD might reflect synaptic loss and disrupted neuronal communication. The medical food Souvenaid, containing the specific nutrient combination Fortasyn

  3. Segmentation of brain parenchymal regions into gray matter and white matter with Alzheimer's disease

    International Nuclear Information System (INIS)

    Tokunaga, Chiaki; Yoshiura, Takashi; Yamashita, Yasuo; Magome, Taiki; Honda, Hiroshi; Arimura, Hidetaka; Toyofuku, Fukai; Ohki, Masafumi

    2010-01-01

    It is very difficult and time consuming for neuroradiologists to estimate the degree of cerebral atrophy based on the volume of cortical regions etc. Our purpose of this study was to develop an automated segmentation of the brain parenchyma into gray and white matter regions with Alzheimer's disease (AD) in three-dimensional (3D) T1-weighted MR images. Our proposed method consisted of extraction of a brain parenchymal region based on a brain model matching and segmentation of the brain parenchyma into gray and white matter regions based on a fuzzy c-means (FCM) algorithm. We applied our proposed method to MR images of the whole brains obtained from 9 cases, including 4 clinically AD cases and 5 control cases. The mean volume percentage of a cortical region (41.7%) to a brain parenchymal region in AD patients was smaller than that (45.2%) in the control subjects (p=0.000462). (author)

  4. Increased blood-brain barrier vulnerability to systemic inflammation in an Alzheimer disease mouse model.

    Science.gov (United States)

    Takeda, Shuko; Sato, Naoyuki; Ikimura, Kazuko; Nishino, Hirohito; Rakugi, Hiromi; Morishita, Ryuichi

    2013-08-01

    Behavioral and psychological problems are often observed in patients with dementia such as that associated with Alzheimer disease, and these noncognitive symptoms place an extremely heavy burden on the family and caregivers. Although it is well know that these symptoms often are triggered by infection of peripheral organs, the underlying mechanisms for these pathological conditions are still unclear. In this study, using an Alzheimer amyloid precursor protein (APP)-transgenic mouse, we analyzed behavioral changes and brain inflammatory response induced by peripheral administration of lipopolysaccharide. Application of a unique in vivo microdialysis system revealed that the increase in brain inflammatory cytokine (interleukin-6) level was significantly higher in APP-Tg than in wild-type mice after peripheral lipopolysaccharide injection, which was associated with more severe sickness behaviors. The blood-brain barrier became more permeable in APP-Tg mice during peripherally evoked inflammation, suggesting the increased vulnerability of the blood-brain barrier to inflammation in this animal model of Alzheimer's disease. These findings might provide insight into the pathogenesis of noncognitive symptoms in dementia and a basis to develop new therapeutic treatments for them. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Mild traumatic brain injury is associated with reduced cortical thickness in those at risk for Alzheimer's disease.

    Science.gov (United States)

    Hayes, Jasmeet P; Logue, Mark W; Sadeh, Naomi; Spielberg, Jeffrey M; Verfaellie, Mieke; Hayes, Scott M; Reagan, Andrew; Salat, David H; Wolf, Erika J; McGlinchey, Regina E; Milberg, William P; Stone, Annjanette; Schichman, Steven A; Miller, Mark W

    2017-03-01

    Moderate-to-severe traumatic brain injury is one of the strongest environmental risk factors for the development of neurodegenerative diseases such as late-onset Alzheimer's disease, although it is unclear whether mild traumatic brain injury, or concussion, also confers risk. This study examined mild traumatic brain injury and genetic risk as predictors of reduced cortical thickness in brain regions previously associated with early Alzheimer's disease, and their relationship with episodic memory. Participants were 160 Iraq and Afghanistan War veterans between the ages of 19 and 58, many of whom carried mild traumatic brain injury and post-traumatic stress disorder diagnoses. Whole-genome polygenic risk scores for the development of Alzheimer's disease were calculated using summary statistics from the largest Alzheimer's disease genome-wide association study to date. Results showed that mild traumatic brain injury moderated the relationship between genetic risk for Alzheimer's disease and cortical thickness, such that individuals with mild traumatic brain injury and high genetic risk showed reduced cortical thickness in Alzheimer's disease-vulnerable regions. Among males with mild traumatic brain injury, high genetic risk for Alzheimer's disease was associated with cortical thinning as a function of time since injury. A moderated mediation analysis showed that mild traumatic brain injury and high genetic risk indirectly influenced episodic memory performance through cortical thickness, suggesting that cortical thinning in Alzheimer's disease-vulnerable brain regions is a mechanism for reduced memory performance. Finally, analyses that examined the apolipoprotein E4 allele, post-traumatic stress disorder, and genetic risk for schizophrenia and depression confirmed the specificity of the Alzheimer's disease polygenic risk finding. These results provide evidence that mild traumatic brain injury is associated with greater neurodegeneration and reduced memory performance

  6. Automatic detection of the hippocampal region associated with Alzheimer's disease from microscopic images of mice brain

    Science.gov (United States)

    Albaidhani, Tahseen; Hawkes, Cheryl; Jassim, Sabah; Al-Assam, Hisham

    2016-05-01

    The hippocampus is the region of the brain that is primarily associated with memory and spatial navigation. It is one of the first brain regions to be damaged when a person suffers from Alzheimer's disease. Recent research in this field has focussed on the assessment of damage to different blood vessels within the hippocampal region from a high throughput brain microscopic images. The ultimate aim of our research is the creation of an automatic system to count and classify different blood vessels such as capillaries, veins, and arteries in the hippocampus region. This work should provide biologists with efficient and accurate tools in their investigation of the causes of Alzheimer's disease. Locating the boundary of the Region of Interest in the hippocampus from microscopic images of mice brain is the first essential stage towards developing such a system. This task benefits from the variation in colour channels and texture between the two sides of the hippocampus and the boundary region. Accordingly, the developed initial step of our research to locating the hippocampus edge uses a colour-based segmentation of the brain image followed by Hough transforms on the colour channel that isolate the hippocampus region. The output is then used to split the brain image into two sides of the detected section of the boundary: the inside region and the outside region. Experimental results on a sufficiently number of microscopic images demonstrate the effectiveness of the developed solution.

  7. Effects of traumatic brain injury and posttraumatic stress disorder on Alzheimer's disease in veterans, using the Alzheimer's Disease Neuroimaging Initiative.

    Science.gov (United States)

    Weiner, Michael W; Veitch, Dallas P; Hayes, Jacqueline; Neylan, Thomas; Grafman, Jordan; Aisen, Paul S; Petersen, Ronald C; Jack, Clifford; Jagust, William; Trojanowski, John Q; Shaw, Leslie M; Saykin, Andrew J; Green, Robert C; Harvey, Danielle; Toga, Arthur W; Friedl, Karl E; Pacifico, Anthony; Sheline, Yvette; Yaffe, Kristine; Mohlenoff, Brian

    2014-06-01

    Both traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are common problems resulting from military service, and both have been associated with increased risk of cognitive decline and dementia resulting from Alzheimer's disease (AD) or other causes. This study aims to use imaging techniques and biomarker analysis to determine whether traumatic brain injury (TBI) and/or PTSD resulting from combat or other traumas increase the risk for AD and decrease cognitive reserve in Veteran subjects, after accounting for age. Using military and Department of Veterans Affairs records, 65 Vietnam War veterans with a history of moderate or severe TBI with or without PTSD, 65 with ongoing PTSD without TBI, and 65 control subjects are being enrolled in this study at 19 sites. The study aims to select subject groups that are comparable in age, gender, ethnicity, and education. Subjects with mild cognitive impairment (MCI) or dementia are being excluded. However, a new study just beginning, and similar in size, will study subjects with TBI, subjects with PTSD, and control subjects with MCI. Baseline measurements of cognition, function, blood, and cerebrospinal fluid biomarkers; magnetic resonance images (structural, diffusion tensor, and resting state blood-level oxygen dependent (BOLD) functional magnetic resonance imaging); and amyloid positron emission tomographic (PET) images with florbetapir are being obtained. One-year follow-up measurements will be collected for most of the baseline procedures, with the exception of the lumbar puncture, the PET imaging, and apolipoprotein E genotyping. To date, 19 subjects with TBI only, 46 with PTSD only, and 15 with TBI and PTSD have been recruited and referred to 13 clinics to undergo the study protocol. It is expected that cohorts will be fully recruited by October 2014. This study is a first step toward the design and statistical powering of an AD prevention trial using at-risk veterans as subjects, and provides the

  8. Nano-enabled drug delivery systems for brain cancer and Alzheimer's disease: research patterns and opportunities.

    Science.gov (United States)

    Ma, Jing; Porter, Alan L; Aminabhavi, Tejraj M; Zhu, Donghua

    2015-10-01

    "Tech mining" applies bibliometric and text analytic methods to scientific literature of a target field. In this study, we compare the evolution of nano-enabled drug delivery (NEDD) systems for two different applications - viz., brain cancer (BC) and Alzheimer's disease (AD) - using this approach. In this process, we derive research intelligence from papers indexed in MEDLINE. Review by domain specialists helps understand the macro-level disease problems and pathologies to identify commonalities and differences between BC and AD. Results provide a fresh perspective on the developmental pathways for NEDD approaches that have been used in the treatment of BC and AD. Results also point toward finding future solutions to drug delivery issues that are critical to medical practitioners and pharmaceutical scientists addressing the brain. Drug delivery to brain cells has been very challenging due to the presence of the blood-brain barrier (BBB). Suitable and effective nano-enabled drug delivery (NEDD) system is urgently needed. In this study, the authors utilized "tech-mining" tools to describe and compare various choices of delivery system available for the diagnosis, as well as treatment, of brain cancer and Alzheimer's disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Integrating Health Promotion Into Physical Therapy Practice to Improve Brain Health and Prevent Alzheimer Disease.

    Science.gov (United States)

    McGough, Ellen; Kirk-Sanchez, Neva; Liu-Ambrose, Teresa

    2017-07-01

    Alzheimer disease is the most common cause of dementia, and brain pathology appears years before symptoms are evident. Primary prevention through health promotion can incorporate lifestyle improvement across the lifespan. Risk factor assessment and identifying markers of disease might also trigger preventive measures needed for high-risk individuals and groups. Many potential risk factors are modifiable through exercise, and may be responsive to early intervention strategies to reduce the downward slope toward disability. Through the use of common clinical tests to identify cognitive and noncognitive functional markers of disease, detection and intervention can occur at earlier stages, including preclinical stages of disease. Physical activity and exercise interventions to address modifiable risk factors and impairments can play a pivotal role in the prevention and delay of functional decline, ultimately reducing the incidence of dementia. This article discusses prevention, prediction, plasticity, and participation in the context of preserving brain health and preventing Alzheimer disease and related dementias in aging adults. Rehabilitation professionals have opportunities to slow disease progression through research, practice, and education initiatives. From a clinical perspective, interventions that target brain health through lifestyle changes and exercise interventions show promise for preventing stroke and associated neurovascular diseases in addition to dementia. Physical therapists are well positioned to integrate primary health promotion into practice for the prevention of dementia and other neurological conditions in older adults.

  10. Useful Information on...Alzheimer's Disease.

    Science.gov (United States)

    Cohen, Gene D.

    This brochure provides information on Alzheimer's disease by examining who gets Alzheimer's disease and what to expect when someone has Alzheimer's disease. Abnormal brain tissue findings are discussed and three clinical features of Alzheimer's disease are listed: dementia; insidious onset of symptoms; and exclusion of all other specific causes of…

  11. GLP-1 analog raises glucose transport capacity of blood-brain barrier in Alzheimer's disease

    DEFF Research Database (Denmark)

    Gejl, M.; Brock, B.; Egefjord, L.

    2017-01-01

    Objectives: Glucose enters the brain tissue from plasma by facilitated diffusion across the two membranes of the endothelium of the blood-brain barrier (BBB), mediated by the glucose transporter 1 (GLUT1). There is evidence in Alzheimer's disease (AD) of reduction of glucose transport across...... the blood-brain barrier, due to diminished GLUT1 translocation and expression at the BBB. Reduced BBB GLUT1 expression is known to aggravate AD pathology and further impair cognitive function, implying that GLUT1 may be a potential target of therapy directed towards AD neurovascular dysfunction...... and degeneration. Hypothesis: The incretin hormone GLP-1 prevents the decline of the cerebral metabolic rate of glucose that signifies cognitive impairment, synaptic dysfunction, and disease evolution in AD, and GLP-1 may directly activate GLUT1 transport in brain capillary endothelium. For this reason, we here...

  12. Ethical Considerations for Deep Brain Stimulation Trials in Patients with Early-Onset Alzheimer's Disease.

    Science.gov (United States)

    Viaña, John Noel M; Bittlinger, Merlin; Gilbert, Frederic

    2017-01-01

    Several studies of deep brain stimulation (DBS) of the fornix or the nucleus basalis of Meynert have been recently conducted in people with Alzheimer's disease, with several recruiting participants early-onset Alzheimer's disease (EOAD). Although EOAD accounts for less than 5.5% of AD cases, ethical considerations must still be made when performing DBS trials including these participants since a portion of people with EOAD, especially those possessing autosomal-dominant mutations, have an atypical and more aggressive disease progression. These considerations include appropriate patient selection and signing of an informed consent for genetic testing; appropriate study design; potential outcomes that people with EOAD could expect; and accurate interpretation and balanced discussion of trial results. Finally, recommendations for future DBS for AD trials will be made to ensure that EOAD patients will not experience avoidable harms should they be enrolled in these experimental studies.

  13. Quiz: Alzheimer's Disease

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Alzheimer's Disease Quiz: Alzheimer's Disease Past Issues / Winter 2015 Table of Contents ... How many Americans over age 65 may have Alzheimer's disease? as many as 5 million as many ...

  14. Alzheimer\\'s Disease: Yesterday, Today, Tomorrow

    Directory of Open Access Journals (Sweden)

    Farid Fadaei

    2007-04-01

    Full Text Available Alzheimer's disease is the most common and well - known cause of dementia, as a progressive, irreversible brain disorder that affects cognitive function, personality, thought, perception and behaviour. Alzheimer's disease is the fourth leading cause of death in western countries. Interesting to know that this disease was unknown in medical community till 100 years ago and had no name. Dr. Alois Alzheimer, a German psychiatrist was the person who suspected the presence of this new illness and by succinct clinical, neuroanatomic, and neuropathologic examination of some cases; including the first known case of this disease- a woman named Auguste Deter- documented it. In further Emil Kraepe1inby knowing about the cases that Dr. Alzheimer reported, and another reports of this disease that were published in the first decade of the twentieth century, set the name of Alzbeimer on this new disease. Descriptions of Dr. Alzheimer and Kraepelin are the same as the present day descriptions of this disease. Electron microscopy, quantitative morphology and modem biochemistry emerging in the second half of the twentieth century opened a new era in dementia research with description of the ultra structure and biochemistry of senileplaques and neuronfibrillary tangles, the major disease markers of Alzheimer's disease. Basic research gave insight into the molecular genetics and pathophysiology of Alzheimers disease and based on the biochemical findings, new pharmacological treatment options were opened. The future attempts will probably be concentrated on the prevention of this disease. Oxidative stress, excessive transition metal ions, and misfolded / aggregated proteins and inflammation are among the probable causes of Alzheimer's disease and the future research will focus on their better understanding and prevention of their occurrence. As the last word, stem cells grafts that in animals have led to remarkable improvement of brain function may also be a

  15. Individuals at risk for Alzheimer's disease show differential patterns of ERP brain activation during odor identification.

    Science.gov (United States)

    Morgan, Charlie D; Murphy, Claire

    2012-07-31

    Studies suggest that older adults at risk of developing Alzheimer's disease may show olfactory processing deficits before other signs of dementia appear. We studied 60 healthy non-demented individuals, half of whom were positive for the genetic risk factor the Apolipoprotein E ε4 allele, in three different age groups. Event-related potentials to visual and olfactory identification tasks were recorded and analyzed for latency and amplitude differences, and plotted via topographical maps. Varying patterns of brain activation were observed over the post-stimulus epoch for ε4- versus ε4+ individuals on topographical maps. Individuals with the ε4 allele demonstrated different ERP peak latencies during identification of olfactory but not visual stimuli. High correct ApoE classification rates were obtained utilizing the olfactory ERP. Olfactory ERPs demonstrate functional decline in individuals at risk for Alzheimer's disease at much earlier ages than previously observed, suggesting the potential for pre-clinical detection of AD at very early stages.

  16. Increased White Matter Inflammation in Aging- and Alzheimer's Disease Brain

    NARCIS (Netherlands)

    Raj, Divya; Yin, Zhuoran; Breur, Marjolein; Doorduin, Janine; Holtman, Inge R.; Olah, Marta; Mantingh-Otter, Ietje J.; Van Dam, Debby; De Deyn, Peter P.; den Dunnen, Wilfred; Eggen, Bart J. L.; Amor, Sandra; Boddeke, Erik

    2017-01-01

    Chronic neuroinflammation, which is primarily mediated by microglia, plays an essential role in aging and neurodegeneration. It is still unclear whether this microglia-induced neuroinflammation occurs globally or is confined to distinct brain regions. In this study, we investigated microglia

  17. Terahertz spectroscopy of brain tissue from a mouse model of Alzheimer's disease

    Science.gov (United States)

    Shi, Lingyan; Shumyatsky, Pavel; Rodríguez-Contreras, Adrián; Alfano, Robert

    2016-01-01

    The terahertz (THz) absorption and index of refraction of brain tissues from a mouse model of Alzheimer's disease (AD) and a control wild-type (normal) mouse were compared using THz time-domain spectroscopy (THz-TDS). Three dominating absorption peaks associated to torsional-vibrational modes were observed in AD tissue, at about 1.44, 1.8, and 2.114 THz, closer to the peaks of free tryptophan molecules than in normal tissue. A possible reason is that there is more free tryptophan in AD brain tissue, while in normal brain tissue more tryptophan is attached to other molecules. Our study suggests that THz-absorption modes may be used as an AD biomarker fingerprint in brain, and that THz-TDS is a promising technique for early diagnosis of AD.

  18. Spectroscopic imaging with spectral domain visible light optical coherence microscopy in Alzheimer's disease brain samples.

    Science.gov (United States)

    Lichtenegger, Antonia; Harper, Danielle J; Augustin, Marco; Eugui, Pablo; Muck, Martina; Gesperger, Johanna; Hitzenberger, Christoph K; Woehrer, Adelheid; Baumann, Bernhard

    2017-09-01

    A visible light spectral domain optical coherence microscopy system was developed. A high axial resolution of 0.88 μm in tissue was achieved using a broad visible light spectrum (425 - 685 nm ). Healthy human brain tissue was imaged to quantify the difference between white (WM) and grey matter (GM) in intensity and attenuation. The high axial resolution enables the investigation of amyloid-beta plaques of various sizes in human brain tissue and animal models of Alzheimer's disease (AD). By performing a spectroscopic analysis of the OCM data, differences in the characteristics for WM, GM, and neuritic amyloid-beta plaques were found. To gain additional contrast, Congo red stained AD brain tissue was investigated. A first effort was made to investigate optically cleared mouse brain tissue to increase the penetration depth and visualize hyperscattering structures in deeper cortical regions.

  19. Conserved brain myelination networks are altered in Alzheimer's and other neurodegenerative diseases.

    Science.gov (United States)

    Allen, Mariet; Wang, Xue; Burgess, Jeremy D; Watzlawik, Jens; Serie, Daniel J; Younkin, Curtis S; Nguyen, Thuy; Malphrus, Kimberly G; Lincoln, Sarah; Carrasquillo, Minerva M; Ho, Charlotte; Chakrabarty, Paramita; Strickland, Samantha; Murray, Melissa E; Swarup, Vivek; Geschwind, Daniel H; Seyfried, Nicholas T; Dammer, Eric B; Lah, James J; Levey, Allan I; Golde, Todd E; Funk, Cory; Li, Hongdong; Price, Nathan D; Petersen, Ronald C; Graff-Radford, Neill R; Younkin, Steven G; Dickson, Dennis W; Crook, Julia R; Asmann, Yan W; Ertekin-Taner, Nilüfer

    2017-10-26

    Comparative transcriptome analyses in Alzheimer's disease (AD) and other neurodegenerative proteinopathies can uncover both shared and distinct disease pathways. We analyzed 940 brain transcriptomes including patients with AD, progressive supranuclear palsy (PSP; a primary tauopathy), and control subjects. We identified transcriptional coexpression networks implicated in myelination, which were lower in PSP temporal cortex (TCX) compared with AD. Some of these associations were retained even after adjustments for brain cell population changes. These TCX myelination network structures were preserved in cerebellum but they were not differentially expressed in cerebellum between AD and PSP. Myelination networks were downregulated in both AD and PSP, when compared with control TCX samples. Downregulation of myelination networks may underlie both PSP and AD pathophysiology, but may be more pronounced in PSP. These data also highlight conservation of transcriptional networks across brain regions and the influence of cell type changes on these networks. Copyright © 2017. Published by Elsevier Inc.

  20. Inflammation and Alzheimer's disease

    NARCIS (Netherlands)

    Akiyama, H.; Barger, S.; Barnum, S.; Bradt, B.; Bauer, J.; Cole, G. M.; Cooper, N. R.; Eikelenboom, P.; Emmerling, M.; Fiebich, B. L.; Finch, C. E.; Frautschy, S.; Griffin, W. S.; Hampel, H.; Hull, M.; Landreth, G.; Lue, L.; Mrak, R.; Mackenzie, I. R.; McGeer, P. L.; O'Banion, M. K.; Pachter, J.; Pasinetti, G.; Plata-Salaman, C.; Rogers, J.; Rydel, R.; Shen, Y.; Streit, W.; Strohmeyer, R.; Tooyoma, I.; van Muiswinkel, F. L.; Veerhuis, R.; Walker, D.; Webster, S.; Wegrzyniak, B.; Wenk, G.; Wyss-Coray, T.

    2000-01-01

    Inflammation clearly occurs in pathologically vulnerable regions of the Alzheimer's disease (AD) brain, and it does so with the full complexity of local peripheral inflammatory responses. In the periphery, degenerating tissue and the deposition of highly insoluble abnormal materials are classical

  1. Antroquinonol Lowers Brain Amyloid-? Levels and Improves Spatial Learning and Memory in a Transgenic Mouse Model of Alzheimer?s Disease

    OpenAIRE

    Chang, Wen-Han; Chen, Miles C.; Cheng, Irene H.

    2015-01-01

    Alzheimer?s disease (AD) is the most common form of dementia. The deposition of brain amyloid-? peptides (A?), which are cleaved from amyloid precursor protein (APP), is one of the pathological hallmarks of AD. A?-induced oxidative stress and neuroinflammation play important roles in the pathogenesis of AD. Antroquinonol, a ubiquinone derivative isolated from Antrodia camphorata, has been shown to reduce oxidative stress and inflammatory cytokines via activating the nuclear transcription fact...

  2. Testosterone effect on brain metabolism in elderly patients with Alzheimer's disease: comparing two cases at different disease stages.

    Science.gov (United States)

    Tan, R S

    2013-06-01

    To describe the effect of testosterone replacement therapy (TRT) on the brain activity of two demented, hypogonadal male patients with early and late-stage Alzheimer's disease (AD), respectively. We describe the clinical and positron emission tomography (PET) findings for two individuals, one with early stage and the other with late-stage Alzheimer's disease, before and after treatment with a topical testosterone gel. Both patients were hypogonadal at baseline. We assessed cerebral glucose metabolism (CGM) via (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET). We investigated whether there are testosterone-susceptible areas within cerebral structures in patients with Alzheimer's disease. Under testosterone replacement therapy, changes in cerebral glucose metabolism were observed in both patients. Improvement in glucose uptake was observed most consistently in the parietal lobe and brainstem; decreased glucose metabolism was observed in the temporal lobe, the limbic system and the insula for these two subjects. These case reports demonstrate the potential for PET scanning to detect changes in cerebral glucose metabolism in hypogonadal men with Alzheimer's disease who are treated with testosterone. Further study will be needed to investigate the consistency and significance of these changes in terms of magnitude and brain region, and the correlation with functional changes.

  3. Epidemiology of Alzheimer Disease

    Science.gov (United States)

    Mayeux, Richard; Stern, Yaakov

    2012-01-01

    The global prevalence of dementia has been estimated to be as high as 24 million, and is predicted to double every 20 years until at least 2040. As the population worldwide continues to age, the number of individuals at risk will also increase, particularly among the very old. Alzheimer disease is the leading cause of dementia beginning with impaired memory. The neuropathological hallmarks of Alzheimer disease include diffuse and neuritic extracellular amyloid plaques in brain that are frequently surrounded by dystrophic neurites and intraneuronal neurofibrillary tangles. The etiology of Alzheimer disease remains unclear, but it is likely to be the result of both genetic and environmental factors. In this review we discuss the prevalence and incidence rates, the established environmental risk factors, and the protective factors, and briefly review genetic variants predisposing to disease. PMID:22908189

  4. Effect of aging and Alzheimer's disease-like pathology on brain monoamines in mice

    DEFF Research Database (Denmark)

    Von Linstow, C. U.; Severino, Maurizio; Metaxas, Athanasios

    2017-01-01

    , but these can both be age- and/or disease-related. We examined whether brain monoamine levels change as part of physiological aging and/or AD-like disease in APPSWE/PS1δE9 (APP/PS1) transgenic mice. The neocortex, hippocampus, striatum, brainstem and cerebellum of 6-, 12-, 18- and 24-month-old B6C3 wild....... In combination, these findings indicate that aging alone is not sufficient to affect brain monoamine levels, unlike the APPSWE/PS1δE9 genotype.......Aging is the greatest single risk factor of the neurodegenerative disorder Alzheimer's disease (AD). The monoaminergic system, including serotonin (5-HT), dopamine (DA) and noradrenaline (NA) modulates cognition, which is affected in AD. Changes in monoamine levels have been observed in AD...

  5. Caffeine blocks disruption of blood brain barrier in a rabbit model of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Ghribi Othman

    2008-04-01

    Full Text Available Abstract High levels of serum cholesterol and disruptions of the blood brain barrier (BBB have all been implicated as underlying mechanisms in the pathogenesis of Alzheimer's disease. Results from studies conducted in animals and humans suggest that caffeine might be protective against Alzheimer's disease but by poorly understood mechanisms. Using rabbits fed a cholesterol-enriched diet, we tested our hypothesis that chronic ingestion of caffeine protects against high cholesterol diet-induced disruptions of the BBB. New Zealand rabbits were fed a 2% cholesterol-enriched diet, and 3 mg caffeine was administered daily in drinking water for 12 weeks. Total cholesterol and caffeine concentrations from blood were measured. Olfactory bulbs (and for some studies hippocampus and cerebral cortex as well were evaluated for BBB leakage, BBB tight junction protein expression levels, activation of astrocytes, and microglia density using histological, immunostaining and immunoblotting techniques. We found that caffeine blocked high cholesterol diet-induced increases in extravasation of IgG and fibrinogen, increases in leakage of Evan's blue dye, decreases in levels of the tight junction proteins occludin and ZO-1, increases in astrocytes activation and microglia density where IgG extravasation was present. Chronic ingestion of caffeine protects against high cholesterol diet-induced increases in disruptions of the BBB, and caffeine and drugs similar to caffeine might be useful in the treatment of Alzheimer's disease.

  6. How Alzheimer's Changes the Brain

    Medline Plus

    Full Text Available ... Disease - Duration: 42:07. All N One Home Health 102,543 views 42:07 Your Amazing Brain - ... Bredesen, MD - Duration: 1:13:27. Silicon Valley Health Institute 95,087 views 1:13:27 Alzheimer's ...

  7. Predicting Alzheimer's disease by classifying 3D-Brain MRI images using SVM and other well-defined classifiers

    International Nuclear Information System (INIS)

    Matoug, S; Abdel-Dayem, A; Passi, K; Gross, W; Alqarni, M

    2012-01-01

    Alzheimer's disease (AD) is the most common form of dementia affecting seniors age 65 and over. When AD is suspected, the diagnosis is usually confirmed with behavioural assessments and cognitive tests, often followed by a brain scan. Advanced medical imaging and pattern recognition techniques are good tools to create a learning database in the first step and to predict the class label of incoming data in order to assess the development of the disease, i.e., the conversion from prodromal stages (mild cognitive impairment) to Alzheimer's disease, which is the most critical brain disease for the senior population. Advanced medical imaging such as the volumetric MRI can detect changes in the size of brain regions due to the loss of the brain tissues. Measuring regions that atrophy during the progress of Alzheimer's disease can help neurologists in detecting and staging the disease. In the present investigation, we present a pseudo-automatic scheme that reads volumetric MRI, extracts the middle slices of the brain region, performs segmentation in order to detect the region of brain's ventricle, generates a feature vector that characterizes this region, creates an SQL database that contains the generated data, and finally classifies the images based on the extracted features. For our results, we have used the MRI data sets from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database.

  8. Predicting Alzheimer's disease by classifying 3D-Brain MRI images using SVM and other well-defined classifiers

    Science.gov (United States)

    Matoug, S.; Abdel-Dayem, A.; Passi, K.; Gross, W.; Alqarni, M.

    2012-02-01

    Alzheimer's disease (AD) is the most common form of dementia affecting seniors age 65 and over. When AD is suspected, the diagnosis is usually confirmed with behavioural assessments and cognitive tests, often followed by a brain scan. Advanced medical imaging and pattern recognition techniques are good tools to create a learning database in the first step and to predict the class label of incoming data in order to assess the development of the disease, i.e., the conversion from prodromal stages (mild cognitive impairment) to Alzheimer's disease, which is the most critical brain disease for the senior population. Advanced medical imaging such as the volumetric MRI can detect changes in the size of brain regions due to the loss of the brain tissues. Measuring regions that atrophy during the progress of Alzheimer's disease can help neurologists in detecting and staging the disease. In the present investigation, we present a pseudo-automatic scheme that reads volumetric MRI, extracts the middle slices of the brain region, performs segmentation in order to detect the region of brain's ventricle, generates a feature vector that characterizes this region, creates an SQL database that contains the generated data, and finally classifies the images based on the extracted features. For our results, we have used the MRI data sets from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database.

  9. Global quantitative analysis of the human brain proteome in Alzheimer's and Parkinson's Disease

    Science.gov (United States)

    Ping, Lingyan; Duong, Duc M.; Yin, Luming; Gearing, Marla; Lah, James J.; Levey, Allan I.; Seyfried, Nicholas T.

    2018-03-01

    Patients with Alzheimer's disease (AD) and Parkinson's disease (PD) often have overlap in clinical presentation and brain neuropathology suggesting that these two diseases share common underlying mechanisms. Currently, the molecular pathways linking AD and PD are incompletely understood. Utilizing Tandem Mass Tag (TMT) isobaric labeling and synchronous precursor selection-based MS3 (SPS-MS3) mass spectrometry, we performed an unbiased quantitative proteomic analysis of post-mortem human brain tissues (n=80) from four different groups defined as controls, AD, PD, and co-morbid AD/PD cases across two brain regions (frontal cortex and anterior cingulate gyrus). In total, we identified 11 840 protein groups representing 10 230 gene symbols, which map to ~65% of the protein coding genes in brain. The utility of including two reference standards in each TMT 10-plex assay to assess intra- and inter-batch variance is also described. Ultimately, this comprehensive human brain proteomic dataset serves as a valuable resource for various research endeavors including, but not limited to, the identification of disease-specific protein signatures and molecular pathways that are common in AD and PD.

  10. Anti-Amyloid-?-Mediated Positron Emission Tomography Imaging in Alzheimer's Disease Mouse Brains

    OpenAIRE

    McLean, Daniel; Cooke, Michael J.; Wang, Yuanfei; Green, David; Fraser, Paul E.; George-Hyslop, Peter St; Shoichet, Molly S.

    2012-01-01

    Antibody-mediated imaging of amyloid β (Aβ) in Alzheimer's disease (AD) offers a promising strategy to detect and monitor specific Aβ species, such as oligomers, that have important pathological and therapeutic relevance. The major current limitation of antibodies as a diagnostic and imaging device is poor blood-brain-barrier permeability. A classical anti-Aβ antibody, 6E10, is modified with 10 kDa polyethylene glycol (PEG) and a positron emitting isotope, Copper-64 (t(½) = 12.7 h), and intra...

  11. Graph analysis of structural brain networks in Alzheimer's disease: beyond small world properties.

    Science.gov (United States)

    John, Majnu; Ikuta, Toshikazu; Ferbinteanu, Janina

    2017-03-01

    Changes in brain connectivity in patients with early Alzheimer's disease (AD) have been investigated using graph analysis. However, these studies were based on small data sets, explored a limited range of network parameters, and did not focus on more restricted sub-networks, where neurodegenerative processes may introduce more prominent alterations. In this study, we constructed structural brain networks out of 87 regions using data from 135 healthy elders and 100 early AD patients selected from the Open Access Series of Imaging Studies (OASIS) database. We evaluated the graph properties of these networks by investigating metrics of network efficiency, small world properties, segregation, product measures of complexity, and entropy. Because degenerative processes take place at different rates in different brain areas, analysis restricted to sub-networks may reveal changes otherwise undetected. Therefore, we first analyzed the graph properties of a network encompassing all brain areas considered together, and then repeated the analysis after dividing the brain areas into two sub-networks constructed by applying a clustering algorithm. At the level of large scale network, the analysis did not reveal differences between AD patients and controls. In contrast, the same analysis performed on the two sub-networks revealed that small worldness diminished with AD only in the sub-network containing the areas of medial temporal lobe known to be heaviest and earliest affected. The second sub-network, which did not present significant AD-induced modifications of 'classical' small world parameters, nonetheless showed a trend towards an increase in small world propensity, a novel metric that unbiasedly quantifies small world structure. Beyond small world properties, complexity and entropy measures indicated that the intricacy of connection patterns and structural diversity decreased in both sub-networks. These results show that neurodegenerative processes impact volumetric

  12. Brain Network Alterations in Alzheimer's Disease Identified by Early-Phase PIB-PET.

    Science.gov (United States)

    Fu, Liping; Liu, Linwen; Zhang, Jinming; Xu, Baixuan; Fan, Yong; Tian, Jiahe

    2018-01-01

    The aim of this study was to identify the brain networks from early-phase 11 C-PIB (perfusion PIB, pPIB) data and to compare the brain networks of patients with differentiating Alzheimer's disease (AD) with cognitively normal subjects (CN) and of mild cognitively impaired patients (MCI) with CN. Forty participants (14 CN, 12 MCI, and 14 AD) underwent 11 C-PIB and 18 F-FDG PET/CT scans. Parallel independent component analysis (pICA) was used to identify correlated brain networks from the 11 C-pPIB and 18 F-FDG data, and a two-sample t -test was used to evaluate group differences in the corrected brain networks between AD and CN, and between MCI and CN. Our study identified a brain network of perfusion (early-phase 11 C-PIB) that highly correlated with a glucose metabolism ( 18 F-FDG) brain network and colocalized with the default mode network (DMN) in an AD-specific neurodegenerative cohort. Particularly, decreased 18 F-FDG uptake correlated with a decreased regional cerebral blood flow in the frontal, parietal, and temporal regions of the DMN. The group comparisons revealed similar spatial patterns of the brain networks derived from the 11 C-pPIB and 18 F-FDG data. Our findings indicate that 11 C-pPIB derived from the early-phase 11 C-PIB could provide complementary information for 18 F-FDG examination in AD.

  13. A Systematic Investigation into Aging Related Genes in Brain and Their Relationship with Alzheimer's Disease.

    Science.gov (United States)

    Meng, Guofeng; Zhong, Xiaoyan; Mei, Hongkang

    2016-01-01

    Aging, as a complex biological process, is accompanied by the accumulation of functional loses at different levels, which makes age to be the biggest risk factor to many neurological diseases. Even following decades of investigation, the process of aging is still far from being fully understood, especially at a systematic level. In this study, we identified aging related genes in brain by collecting the ones with sustained and consistent gene expression or DNA methylation changes in the aging process. Functional analysis with Gene Ontology to these genes suggested transcriptional regulators to be the most affected genes in the aging process. Transcription regulation analysis found some transcription factors, especially Specificity Protein 1 (SP1), to play important roles in regulating aging related gene expression. Module-based functional analysis indicated these genes to be associated with many well-known aging related pathways, supporting the validity of our approach to select aging related genes. Finally, we investigated the roles of aging related genes on Alzheimer's Disease (AD). We found that aging and AD related genes both involved some common pathways, which provided a possible explanation why aging made the brain more vulnerable to Alzheimer's Disease.

  14. A Long Journey into Aging, Brain Aging, and Alzheimer's Disease Following the Oxidative Stress Tracks.

    Science.gov (United States)

    Mecocci, Patrizia; Boccardi, Virginia; Cecchetti, Roberta; Bastiani, Patrizia; Scamosci, Michela; Ruggiero, Carmelinda; Baroni, Marta

    2018-01-01

    The Editors of the Journal of Alzheimer's Disease invited Professor Patrizia Mecocci to contribute a review article focused on the importance and implications of her research on aging, brain aging, and senile dementias over the last years. This invitation was based on an assessment that she was one of the journal's top authors and a strong supporter of the concept that oxidative stress is a major contributor to several alterations observed in age-related conditions (sarcopenia, osteoporosis) and, more significantly, in brain aging suggesting a pivotal role in the pathogenesis and progression of one of the most dramatic age-related diseases, Alzheimer's disease (AD). Her first pioneering research was on the discovery of high level of 8-hydroxy-2'-deoxyguanosine (OH8dG), a marker of oxidation in nucleic acids, in mitochondrial DNA isolated from cerebral cortex. This molecule increases progressively with aging and more in AD brain, supporting the hypothesis that oxidative stress, a condition of unbalance between the production of reactive oxygen species and antioxidants, gives a strong contribution to the high incidence of AD in old age subjects. OH8dG also increases in peripheral lymphocyte from AD subjects, suggesting that AD is not only a cerebral but also a systemic disease. The role of antioxidants, particularly vitamin E and zinc, were also studied in longevity and in cognitive decline and dementia. This review shows the main findings from Mecocci's laboratory related to oxidative stress in aging, brain aging, and AD and discusses the importance and implications of some of the major achievements in this field of research.

  15. Exosomal biomarkers of brain insulin resistance associated with regional atrophy in Alzheimer's disease.

    Science.gov (United States)

    Mullins, Roger J; Mustapic, Maja; Goetzl, Edward J; Kapogiannis, Dimitrios

    2017-04-01

    Brain insulin resistance (IR), which depends on insulin-receptor-substrate-1 (IRS-1) phosphorylation, is characteristic of Alzheimer's disease (AD). Previously, we demonstrated higher pSer312-IRS-1 (ineffective insulin signaling) and lower p-panTyr-IRS-1 (effective insulin signaling) in neural origin-enriched plasma exosomes of AD patients vs. Here, we hypothesized that these exosomal biomarkers associate with brain atrophy in AD. We studied 24 subjects with biomarker-supported probable AD (low CSF Aβ 42 ). Exosomes were isolated from plasma, enriched for neural origin using immunoprecipitation for L1CAM, and measured for pSer 312 - and p-panTyr-IRS-1 phosphotypes. MPRAGE images were segmented by brain tissue type and voxel-based morphometry (VBM) analysis for gray matter against pSer 312 - and p-panTyr-IRS-1 was conducted. Given the regionally variable brain expression of IRS-1, we used the Allen Brain Atlas to make spatial comparisons between VBM results and IRS-1 expression. Brain volume was positively associated with P-panTyr-IRS-1 and negatively associated with pSer 312 -IRS-1 in a strikingly similar regional pattern (bilateral parietal-occipital junction, R middle temporal gyrus). This volumetric association pattern was spatially correlated with Allen Human Brain atlas normal brain IRS-1 expression. Exosomal biomarkers of brain IR are thus associated with atrophy in AD as could be expected by their pathophysiological roles and do so in a pattern that reflects regional IRS-1 expression. Furthermore, neural-origin plasma exosomes may recover molecular signals from specific brain regions. Hum Brain Mapp 38:1933-1940, 2017. © 2017 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. Alzheimer's disease neuropathologic change, Lewy body disease, and vascular brain injury in clinic- and community-based samples.

    Science.gov (United States)

    Brenowitz, Willa D; Keene, C Dirk; Hawes, Stephen E; Hubbard, Rebecca A; Longstreth, W T; Woltjer, Randy L; Crane, Paul K; Larson, Eric B; Kukull, Walter A

    2017-05-01

    We examined the relationships between Alzheimer's disease neuropathologic change (ADNC), Lewy body disease (LBD), and vascular brain injury (VBI) in 2 large autopsy samples. Because findings may differ between study populations, data came from U.S. Alzheimer's Disease Centers contributing to the National Alzheimer's Coordinating Center (n = 2742) and from the population-based Adult Changes in Thought study (n = 499). Regardless of study population, over 50% of participants with ADNC had co-occurring LBD or VBI; the majority of whom had a clinical AD dementia diagnosis prior to death. Overlap of pathologies was similar between studies, especially after standardizing to the distribution of age and dementia status in the Adult Changes in Thought population. LBD, but not VBI, was positively associated with ADNC in both studies. Interestingly, cortical LBD was more common in those with intermediate ADNC compared to low or high ADNC, especially in the National Alzheimer's Coordinating Center (p < 0.001). High prevalence of co-occurring neuropathologies among older adults with dementia has implications for accurate diagnosis of dementia etiologies and development of disease-modifying strategies. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. The preliminary study of 18F-FDG brain PET in diagnosis of alzheimer's disease

    International Nuclear Information System (INIS)

    Ma Yunchuan; Zhang Xinqing; Li Depeng; Shang Jianwen; Su Yusheng; Zhang Linying; Peng Cheng; Pan Zhongyun

    2000-01-01

    Objective: To investigate the imaging characteristics and diagnostic criteria of 18 F-FDG brain PET in diagnosis of Alzheimer's disease (AD). Methods: The sutdy included 12 normal subjects, 12 patients with AD and 11 patients with non-AD dementia. 40 min after intravenous administration of 18 F-FDG, brain scan was performed using Siemens ECAT47 scanner. The transaxial, coronal and sagittal images were then reconstructed by computer. At the same time, semiquantitative analysis was also applied to help evaluation using the ratio of mean radioactivity of cerebral lobe to cerebellum (R cl/cb ). Results: In normal subjects PET scan showed clear images of cerebral cortex, basal ganglia, thalamus and cerebellum with symmetrical distribution of radioactivity. PET images from Alzheimer's disease patients were classified into 3 patterns: bilateral parietal hypometabolism in 5 cases, bilateral temporo-parietal hypometabolism in 4 cases and unilateral temporo-parietal hypometabolism in 3 cases. The R cl/cb of AD patients in parietal and temporal lobe was significantly decreased than normal subjects (P cl/cb was also reflecting thedementia degree. Compared with MRI imaging , 12 patients with AD had cerebral hypometabolism but only 10 had hippocampus atrophy. 10 patients with non-AD dementia had local structural foci seen in MRI, including old hemorrhage, infarction and encephalomalacia, but these lesions were not found in AD. Conclusions: Based on excluding cerebral structural lesions which are better detected by MRI, bilateral or unilateral parietal or temporo-parietal hypometabolism found in FDG PET can be considered indicative of Alzheimer's disease. Semiquantitative analysis of the images yielded can help to evaluate the dementia degree

  18. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... that use detectable measures of biological changes in the brain, commonly known as biological markers, or biomarkers, as part of the diagnosis. The development and validation of Alzheimer's disease ...

  19. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... arc of scientific progress is now requiring a change in how we diagnose Alzheimer's disease. Both the ... proposed guidelines that use detectable measures of biological changes in the brain, commonly known as biological markers, ...

  20. Classification of Alzheimer's disease using regional saliency maps from brain MR volumes

    Science.gov (United States)

    Pulido, Andrea; Rueda, Andrea; Romero, Eduardo

    2013-02-01

    Accurate diagnosis of Alzheimer's disease (AD) from structural Magnetic Resonance (MR) images is difficult due to the complex alteration of patterns in brain anatomy that could indicate the presence or absence of the pathology. Currently, an effective approach that allows to interpret the disease in terms of global and local changes is not available in the clinical practice. In this paper, we propose an approach for classification of brain MR images, based on finding pathology-related patterns through the identification of regional structural changes. The approach combines a probabilistic Latent Semantic Analysis (pLSA) technique, which allows to identify image regions through latent topics inferred from the brain MR slices, with a bottom-up Graph-Based Visual Saliency (GBVS) model, which calculates maps of relevant information per region. Regional saliency maps are finally combined into a single map on each slice, obtaining a master saliency map of each brain volume. The proposed approach includes a one-to-one comparison of the saliency maps which feeds a Support Vector Machine (SVM) classifier, to group test subjects into normal or probable AD subjects. A set of 156 brain MR images from healthy (76) and pathological (80) subjects, splitted into a training set (10 non-demented and 10 demented subjects) and one testing set (136 subjects), was used to evaluate the performance of the proposed approach. Preliminary results show that the proposed method reaches a maximum classification accuracy of 87.21%.

  1. Anti-amyloid-β-mediated positron emission tomography imaging in Alzheimer's disease mouse brains.

    Directory of Open Access Journals (Sweden)

    Daniel McLean

    Full Text Available Antibody-mediated imaging of amyloid β (Aβ in Alzheimer's disease (AD offers a promising strategy to detect and monitor specific Aβ species, such as oligomers, that have important pathological and therapeutic relevance. The major current limitation of antibodies as a diagnostic and imaging device is poor blood-brain-barrier permeability. A classical anti-Aβ antibody, 6E10, is modified with 10 kDa polyethylene glycol (PEG and a positron emitting isotope, Copper-64 (t(½ = 12.7 h, and intravenously delivered to the TgCRND8 mouse model of Alzheimer's disease. Modification of 6E10 with PEG (6E10-PEG increases accumulation of 6E10 in brain tissue in both TgCRND8 and wild type control animals. 6E10-PEG differentiates TgCRND8 animals from wild type controls using positron emission tomography (PET and provides a framework for using antibodies to detect pathology using non-invasive medical imaging techniques.

  2. Characterizing brain patterns in conversion from mild cognitive impairment (MCI) to Alzheimer's disease

    Science.gov (United States)

    Silva R., Santiago S.; Giraldo, Diana L.; Romero, Eduardo

    2017-11-01

    Structural Magnetic Resonance (MR) brain images should provide quantitative information about the stage and progression of Alzheimer's disease. However, the use of MRI is limited and practically reduced to corroborate a diagnosis already performed with neuropsychological tools. This paper presents an automated strategy for extraction of relevant anatomic patterns related with the conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD) using T1-weighted MR images. The process starts by representing each of the possible classes with models generated from a linear combination of volumes. The difference between models allows us to establish which are the regions where relevant patterns might be located. The approach searches patterns in a space of brain sulci, herein approximated by the most representative gradients found in regions of interest defined by the difference between the linear models. This hypothesis is assessed by training a conventional SVM model with the found relevant patterns under a leave-one-out scheme. The resultant AUC was 0.86 for the group of women and 0.61 for the group of men.

  3. Brain alpha-amylase - a novel energy regulator important in Alzheimer disease?

    Science.gov (United States)

    Byman, Elin; Schultz, Nina; Fex, Malin; Wennström, Malin

    2018-02-27

    Reduced glucose metabolism and formation of polyglucosan bodies (PGB) are, beside amyloid beta plaques and neurofibrillary tangles, well-known pathological findings associated with Alzheimer's disease (AD). Since both glucose availability and PGB are regulated by enzymatic degradation of glycogen, we hypothesize that dysfunctional glycogen degradation is a critical event in AD progression. We therefore investigated whether alpha (α)-amylase, an enzyme known to efficiently degrade polysaccharides in the gastrointestinal tract, is expressed in the hippocampal CA1/subiculum and if the expression is altered in AD patients. Using immunohistochemical staining techniques, we show the presence of the α-amylase isotypes AMY1A and AMY2A in neuronal dendritic spines, pericytes and astrocytes. Moreover, AD patients showed reduced gene expression of α-amylase, but conversely increased protein levels of α-amylase as well as increased activity of the enzyme compared to non-demented controls. Lastly, we observed increased, albeit not significant, load of periodic acid-Schiff positive PGB in the brain of AD patients, which correlated with increased α-amylase activity. These findings show that α-amylase is expressed and active in the human brain, and suggest the enzyme to be affected, alternatively play a role, in the neurodegenerative Alzheimer's disease pathology. This article is protected by copyright. All rights reserved. © 2018 International Society of Neuropathology.

  4. Lipid alterations in lipid rafts from Alzheimer's disease human brain cortex.

    Science.gov (United States)

    Martín, Virginia; Fabelo, Noemí; Santpere, Gabriel; Puig, Berta; Marín, Raquel; Ferrer, Isidre; Díaz, Mario

    2010-01-01

    Lipid rafts are membrane microdomains intimately associated with cell signaling. These biochemical microstructures are characterized by their high contents of sphingolipids, cholesterol and saturated fatty acids and a reduced content of polyunsaturated fatty acids (PUFA). Here, we have purified lipid rafts of human frontal brain cortex from normal and Alzheimer's disease (AD) and characterized their biochemical lipid composition. The results revealed that lipid rafts from AD brains exhibit aberrant lipid profiles compared to healthy brains. In particular, lipid rafts from AD brains displayed abnormally low levels of n-3 long chain polyunsaturated fatty acids (LCPUFA, mainly 22:6n-3, docosahexaenoic acid) and monoenes (mainly 18:1n-9, oleic acid), as well as reduced unsaturation and peroxidability indexes. Also, multiple relationships between phospholipids and fatty acids were altered in AD lipid rafts. Importantly, no changes were observed in the mole percentage of lipid classes and fatty acids in rafts from normal brains throughout the lifespan (24-85 years). These indications point to the existence of homeostatic mechanisms preserving lipid raft status in normal frontal cortex. The disruption of such mechanisms in AD brains leads to a considerable increase in lipid raft order and viscosity, which may explain the alterations in lipid raft signaling observed in AD.

  5. Is Alzheimer's Disease Autoimmune Inflammation of the Brain That Can be Treated With Nasal Nonsteroidal Anti-Inflammatory Drugs?

    Science.gov (United States)

    Lehrer, Steven; Rheinstein, Peter H

    2015-05-01

    The Alzheimer's Association recently reported that a woman's estimated lifetime risk of developing Alzheimer's at age 65 is 1 in 6, compared to nearly 1 in 11 for a man (ie, female to male ratio 1.8). Based on female to male ratio, Alzheimer's disease could well be an autoimmune disorder. Like Alzheimer's, multiple sclerosis, an autoimmune inflammation of the central nervous system, has a female to male ratio of 2.3. Also based on female to male ratio, Alzheimer's resembles the autoimmune inflammatory disease rheumatoid arthritis, which has a female to male ratio of 2.7. The reasons for the female preponderance in autoimmune disease are unclear, but nonsteroidal anti-inflammatory drugs (NSAIDs) are widely and successfully employed to treat autoimmune anti-inflammatory disease and dramatically relieve symptoms. Moreover, oral NSAIDs consistently reduce the risk of Alzheimer's disease, although they have been totally ineffective as a treatment in multiple failed clinical trials. A basis for this failure might well be that the brain dose after oral administration is too small and not sufficiently early in the pathogenesis of the disorder. But NSAID brain dose could be significantly increased by delivering the NSAIDs intranasally. © The Author(s) 2014.

  6. Understanding the Connection Between Traumatic Brain Injury and Alzheimer’s Disease: A Population Based Medical Record Review Analysis

    Science.gov (United States)

    2016-10-01

    AWARD NUMBER: W81XWH-15-1-0573 TITLE: Understanding the Connection Between Traumatic Brain Injury and Alzheimer’s Disease: A Population -Based...Sep 2015 - 14 Sep 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Understanding the Connection Between Traumatic Brain Injury and Alzheimer’s Disease...A Population -Based Medical Record Review Analysis 5b. GRANT NUMBER W81XWH-15-1-0573 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Allen W. Brown 5d

  7. Markers of microglia in post-mortem brain samples from patients with Alzheimer's disease: a systematic review.

    Science.gov (United States)

    Hopperton, K E; Mohammad, D; Trépanier, M O; Giuliano, V; Bazinet, R P

    2018-02-01

    Neuroinflammation is proposed as one of the mechanisms by which Alzheimer's disease pathology, including amyloid-β plaques, leads to neuronal death and dysfunction. Increases in the expression of markers of microglia, the main neuroinmmune cell, are widely reported in brains from patients with Alzheimer's disease, but the literature has not yet been systematically reviewed to determine whether this is a consistent pathological feature. A systematic search was conducted in Medline, Embase and PsychINFO for articles published up to 23 February 2017. Papers were included if they quantitatively compared microglia markers in post-mortem brain samples from patients with Alzheimer's disease and aged controls without neurological disease. A total of 113 relevant articles were identified. Consistent increases in markers related to activation, such as major histocompatibility complex II (36/43 studies) and cluster of differentiation 68 (17/21 studies), were identified relative to nonneurological aged controls, whereas other common markers that stain both resting and activated microglia, such as ionized calcium-binding adaptor molecule 1 (10/20 studies) and cluster of differentiation 11b (2/5 studies), were not consistently elevated. Studies of ionized calcium-binding adaptor molecule 1 that used cell counts almost uniformly identified no difference relative to control, indicating that increases in activation occurred without an expansion of the total number of microglia. White matter and cerebellum appeared to be more resistant to these increases than other brain regions. Nine studies were identified that included high pathology controls, patients who remained free of dementia despite Alzheimer's disease pathology. The majority (5/9) of these studies reported higher levels of microglial markers in Alzheimer's disease relative to controls, suggesting that these increases are not solely a consequence of Alzheimer's disease pathology. These results show that increased markers

  8. Synaptic Tau Seeding Precedes Tau Pathology in Human Alzheimer's Disease Brain

    Directory of Open Access Journals (Sweden)

    Sarah L. DeVos

    2018-04-01

    Full Text Available Alzheimer's disease (AD is defined by the presence of intraneuronal neurofibrillary tangles (NFTs composed of hyperphosphorylated tau aggregates as well as extracellular amyloid-beta plaques. The presence and spread of tau pathology through the brain is classified by Braak stages and thought to correlate with the progression of AD. Several in vitro and in vivo studies have examined the ability of tau pathology to move from one neuron to the next, suggesting a “prion-like” spread of tau aggregates may be an underlying cause of Braak tau staging in AD. Using the HEK293 TauRD-P301S-CFP/YFP expressing biosensor cells as a highly sensitive and specific tool to identify the presence of seed competent aggregated tau in brain lysate—i.e., tau aggregates that are capable of recruiting and misfolding monomeric tau—, we detected substantial tau seeding levels in the entorhinal cortex from human cases with only very rare NFTs, suggesting that soluble tau aggregates can exist prior to the development of overt tau pathology. We next looked at tau seeding levels in human brains of varying Braak stages along six regions of the Braak Tau Pathway. Tau seeding levels were detected not only in the brain regions impacted by pathology, but also in the subsequent non-pathology containing region along the Braak pathway. These data imply that pathogenic tau aggregates precede overt tau pathology in a manner that is consistent with transneuronal spread of tau aggregates. We then detected tau seeding in frontal white matter tracts and the optic nerve, two brain regions comprised of axons that contain little to no neuronal cell bodies, implying that tau aggregates can indeed traverse along axons. Finally, we isolated cytosolic and synaptosome fractions along the Braak Tau Pathway from brains of varying Braak stages. Phosphorylated and seed competent tau was significantly enriched in the synaptic fraction of brain regions that did not have extensive cellular tau

  9. Bilingualism as a contributor to cognitive reserve: evidence from brain atrophy in Alzheimer's disease.

    Science.gov (United States)

    Schweizer, Tom A; Ware, Jenna; Fischer, Corinne E; Craik, Fergus I M; Bialystok, Ellen

    2012-09-01

    Much of the research on delaying the onset of symptoms of Alzheimer's disease (AD) has focused on pharmacotherapy, but environmental factors have also been acknowledged to play a significant role. Bilingualism may be one factor contributing to 'cognitive reserve' (CR) and therefore to a delay in symptom onset. If bilingualism is protective, then the brains of bilinguals should show greater atrophy in relevant areas, since their enhanced CR enables them to function at a higher level than would be predicted from their level of disease. We analyzed a number of linear measurements of brain atrophy from the computed tomography (CT) scans of monolingual and bilingual patients diagnosed with probable AD who were matched on level of cognitive performance and years of education. Bilingual patients with AD exhibited substantially greater amounts of brain atrophy than monolingual patients in areas traditionally used to distinguish AD patients from healthy controls, specifically, the radial width of the temporal horn and the temporal horn ratio. Other measures of brain atrophy were comparable for the two groups. Bilingualism appears to contribute to increased CR, thereby delaying the onset of AD and requiring the presence of greater amounts of neuropathology before the disease is manifest. Copyright © 2011 Elsevier Srl. All rights reserved.

  10. Alzheimer disease alters the relationship of cardiorespiratory fitness with brain activity during the stroop task.

    Science.gov (United States)

    Vidoni, Eric D; Gayed, Matthew R; Honea, Robyn A; Savage, Cary R; Hobbs, Derek; Burns, Jeffrey M

    2013-07-01

    Despite mounting evidence that physical activity has positive benefits for brain and cognitive health, there has been little characterization of the relationship between cardiorespiratory (CR) fitness and cognition-associated brain activity as measured by functional magnetic resonance imaging (fMRI). The lack of evidence is particularly glaring for diseases such as Alzheimer disease (AD) that degrade cognitive and functional performance. The aim of this study was to describe the relationship between regional brain activity during cognitive tasks and CR fitness level in people with and without AD. A case-control, single-observation study design was used. Thirty-four individuals (18 without dementia and 16 in the earliest stages of AD) completed maximal exercise testing and performed a Stroop task during fMRI. Cardiorespiratory fitness was inversely associated with anterior cingulate activity in the participants without dementia (r=-.48, P=.05) and unassociated with activation in those with AD (P>.7). Weak associations of CR fitness and middle frontal cortex were noted. The wide age range and the use of a single task in fMRI rather than multiple tasks challenging different cognitive capacities were limitations of the study. The results offer further support of the relationship between CR fitness and regional brain activity. However, this relationship may be attenuated by disease. Future work in this area may provide clinicians and researchers with interpretable and dependable regional fMRI biomarker signatures responsive to exercise intervention. It also may shed light on mechanisms by which exercise can support cognitive function.

  11. Brain MRI, Apoliprotein E Genotype, and Plasma Homocysteine in American Indian Alzheimer Disease Patients and Indian Controls

    OpenAIRE

    Weiner, Myron F.; de la Plata, Carlos Marquez; Fields, B.A. Julie; Womack, Kyle B.; Rosenberg, Roger N.; Gong, Yun-Hua; Qu, Bao-Xi; Diaz-Arrastia, Ramon; Hynan, Linda S.

    2009-01-01

    We obtained brain MRIs, plasma homocysteine levels and apolipoprotein E genotyping for 11 American Indian Alzheimer disease (AD) subjects and 10 Indian controls. We calculated white matter hyperintensity volume (WMHV), whole brain volume (WBV), and ratio of white matter hyperintensity volume to whole brain volume (WMHV/WBV). There were no significant differences between AD subjects and controls in gender, history of hypertension, diabetes, or history of high cholesterol, but hypertension and ...

  12. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... diagnose Alzheimer's disease. Both the National Institute on Aging – Alzheimer's Association (NIA-AA) 2011 workgroup and the International Work Group (IWG) have proposed guidelines that use detectable measures of biological changes in the brain, commonly known as biological markers, ...

  13. The Correlations Between Postmortem Brain Pathologies and Cognitive Dysfunction in Aging and Alzheimer's Disease.

    Science.gov (United States)

    Qiu, Wen-Ying; Yang, Qian; Zhang, Wanying; Wang, Naili; Zhang, Di; Huang, Yue; Ma, Chao

    2017-11-06

    Background The pathological diagnostic criteria for Alzheimer's disease (AD) updated by National Institute on Aging-Alzheimer's Association (NIA-AA) in 2012 has been widely adopted, but the clinicopathological relevance remained obscure in Chinese population. Objective This study aims to investigate the correlations between the antemortem clinical cognitive performances and the postmortem neuropathological changes in the aging and AD brains collected in a human brain bank in China. Method A total of 52 human brains with antemortem cognitive status information [Everyday Cognition (ECog)] were collected through the willed donation program by CAMS/PUMC Human Brain Bank. Pathological changes were evaluated with the "ABC" score following the guidelines of NIA-AA. The clinicopathological relationship was analyzed with correlation analysis and general linear multivariate model. Results The general ABC score has a significant correlation with global ECog score (r=0.37, p=0.014) and most of ECog domains. The CERAD score of neuritic plaques (C score) has a significant correlation with global ECog score (r=0.40, p=0.007) and the majority of ECog domains, such as memory (r=0.50, p=0.001), language (r=0.45, p=0.002), visuospatial functions (r=0.31, p=0.040), planning (r=0.35, p=0.021) and organization (r=0.39, p=0.010). The Braak stage of neurofibrillary tangles (NFTs) (B score) has a moderate correlation with memory (r=0.32, p=0.035). The Thal phases of amyloid-β (Aβ) deposits (A score) presents no significant correlation with any of ECog domains. Conclusion In this study, we verified the correlation of postmortem C and B scores, but not the A score with cognition performance in a collection of samples from the Chinese human brain bank. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Alzheimer's Disease Information Page

    Science.gov (United States)

    ... the National Library of Medicine’s MedlinePlus Alzheimer's Disease Alzheimer's Caregivers × What research is being done? The National Institute ... the National Library of Medicine’s MedlinePlus Alzheimer's Disease Alzheimer's Caregivers See More About Research The National Institute of ...

  15. Preliminary study of Alzheimer's Disease diagnosis based on brain electrical signals using wireless EEG

    Science.gov (United States)

    Handayani, N.; Akbar, Y.; Khotimah, S. N.; Haryanto, F.; Arif, I.; Taruno, W. P.

    2016-03-01

    This research aims to study brain's electrical signals recorded using EEG as a basis for the diagnosis of patients with Alzheimer's Disease (AD). The subjects consisted of patients with AD, and normal subjects are used as the control. Brain signals are recorded for 3 minutes in a relaxed condition and with eyes closed. The data is processed using power spectral analysis, brain mapping and chaos test to observe the level of complexity of EEG's data. The results show a shift in the power spectral in the low frequency band (delta and theta) in AD patients. The increase of delta and theta occurs in lobus frontal area and lobus parietal respectively. However, there is a decrease of alpha activity in AD patients where in the case of normal subjects with relaxed condition, brain alpha wave dominates the posterior area. This is confirmed by the results of brain mapping. While the results of chaos analysis show that the average value of MMLE is lower in AD patients than in normal subjects. The level of chaos associated with neural complexity in AD patients with lower neural complexity is due to neuronal damage caused by the beta amyloid plaques and tau protein in neurons.

  16. Amyloid binding properties of curcumin analogues in Alzheimer's disease postmortem brain tissue.

    Science.gov (United States)

    Veldman, Emma R; Jia, Zhisheng; Halldin, Christer; Svedberg, Marie M

    2016-09-06

    The presence of β-amyloid (Aβ) containing plaques in the brain is a hallmark of Alzheimer's disease (AD) and serves as a biomarker for confirmation of diagnosis postmortem. Early diagnosis is of great importance for optimal treatment and for monitoring disease progression in the brain. Highly specific and sensitive biomarkers are thus greatly needed to assess therapeutic efficacy, not only clinically, but also in terms of clearance of histopathological lesions and decelerated neurodegeneration. The objective of the present study was to give more insight into the binding of curcumin analogues, curcuminoids, to Aβ containing plaques in postmortem tissue from AD patients. In vitro autoradiography was utilized to explore affinity and displacement of the curcuminoids; curcumin, demethoxycurcumin (DMC), bisdemethoxycurcumin (BDMC) and dimethoxycurcumin (DIMC). We found that BDMC had the highest affinity for Aβ containing plaques in cortical AD brain tissue in comparison to other curcuminoids. Subsequently, [(3)H]BDMC showed significantly higher specific binding in cortical AD brain tissue compared to control subjects. These findings suggest that curcumin analogues, especially BDMC, may serve as a potential radioligands for Aβ plaque neuroimaging. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Recent Developments in Understanding Brain Aging: Implications for Alzheimer's Disease and Vascular Cognitive Impairment.

    Science.gov (United States)

    Deak, Ferenc; Freeman, Willard M; Ungvari, Zoltan; Csiszar, Anna; Sonntag, William E

    2016-01-01

    As the population of the Western world is aging, there is increasing awareness of age-related impairments in cognitive function and a rising interest in finding novel approaches to preserve cerebral health. A special collection of articles in The Journals of Gerontology: Biological Sciences and Medical Sciences brings together information of different aspects of brain aging, from latest developments in the field of neurodegenerative disorders to cerebral microvascular mechanisms of cognitive decline. It is emphasized that although the cellular changes that occur within aging neurons have been widely studied, more research is required as new signaling pathways are discovered that can potentially protect cells. New avenues for research targeting cellular senescence, epigenetics, and endocrine mechanisms of brain aging are also discussed. Based on the current literature it is clear that understanding brain aging and reducing risk for neurological disease with age requires searching for mechanisms and treatment options beyond the age-related changes in neuronal function. Thus, comprehensive approaches need to be developed that address the multiple, interrelated mechanisms of brain aging. Attention is brought to the importance of maintenance of cerebromicrovascular health, restoring neuroendocrine balance, and the pressing need for funding more innovative research into the interactions of neuronal, neuroendocrine, inflammatory and microvascular mechanisms of cognitive impairment, and Alzheimer's disease. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. Automated diagnosis of Alzheimer's disease with multi-atlas based whole brain segmentations

    Science.gov (United States)

    Luo, Yuan; Tang, Xiaoying

    2017-03-01

    Voxel-based analysis is widely used in quantitative analysis of structural brain magnetic resonance imaging (MRI) and automated disease detection, such as Alzheimer's disease (AD). However, noise at the voxel level may cause low sensitivity to AD-induced structural abnormalities. This can be addressed with the use of a whole brain structural segmentation approach which greatly reduces the dimension of features (the number of voxels). In this paper, we propose an automatic AD diagnosis system that combines such whole brain segmen- tations with advanced machine learning methods. We used a multi-atlas segmentation technique to parcellate T1-weighted images into 54 distinct brain regions and extract their structural volumes to serve as the features for principal-component-analysis-based dimension reduction and support-vector-machine-based classification. The relationship between the number of retained principal components (PCs) and the diagnosis accuracy was systematically evaluated, in a leave-one-out fashion, based on 28 AD subjects and 23 age-matched healthy subjects. Our approach yielded pretty good classification results with 96.08% overall accuracy being achieved using the three foremost PCs. In addition, our approach yielded 96.43% specificity, 100% sensitivity, and 0.9891 area under the receiver operating characteristic curve.

  19. Fine-mapping the effects of Alzheimer's disease risk loci on brain morphology.

    Science.gov (United States)

    Roshchupkin, Gennady V; Adams, Hieab H; van der Lee, Sven J; Vernooij, Meike W; van Duijn, Cornelia M; Uitterlinden, Andre G; van der Lugt, Aad; Hofman, Albert; Niessen, Wiro J; Ikram, Mohammad A

    2016-12-01

    The neural substrate of genetic risk variants for Alzheimer's disease (AD) remains unknown. We studied their effect on healthy brain morphology to provide insight into disease etiology in the preclinical phase. We included 4071 nondemented, elderly participants of the population-based Rotterdam Study who underwent brain magnetic resonance imaging and genotyping. We performed voxel-based morphometry (VBM) on all gray-matter voxels for 19 previously identified, common AD risk variants. Whole-brain expression data from the Allen Human Brain Atlas was used to examine spatial overlap between VBM association results and expression of genes in AD risk loci regions. Brain regions most significantly associated with AD risk variants were the left postcentral gyrus with ABCA7 (rs4147929, p = 4.45 × 10 -6 ), right superior frontal gyrus by ZCWPW1 (rs1476679, p = 5.12 × 10 -6 ), and right postcentral gyrus by APOE (p = 6.91 × 10 -6 ). Although no individual voxel passed multiple-testing correction, we found significant spatial overlap between the effects of AD risk loci on VBM and the expression of genes (MEF2C, CLU, and SLC24A4) in the Allen Brain Atlas. Results are available online on www.imagene.nl/ADSNPs/. In this single largest imaging genetics data set worldwide, we found that AD risk loci affect cortical gray matter in several brain regions known to be involved in AD, as well as regions that have not been implicated before. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. A putative Alzheimer's disease risk allele in PCK1 influences brain atrophy in multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Zongqi Xia

    2010-11-01

    Full Text Available Brain atrophy and cognitive dysfunction are neurodegenerative features of Multiple Sclerosis (MS. We used a candidate gene approach to address whether genetic variants implicated in susceptibility to late onset Alzheimer's Disease (AD influence brain volume and cognition in MS patients.MS subjects were genotyped for five single nucleotide polymorphisms (snps associated with susceptibility to AD: PICALM, CR1, CLU, PCK1, and ZNF224. We assessed brain volume using Brain Parenchymal Fraction (BPF measurements obtained from Magnetic Resonance Imaging (MRI data and cognitive function using the Symbol Digit Modalities Test (SDMT. Genotypes were correlated with cross-sectional BPF and SDMT scores using linear regression after adjusting for sex, age at symptom onset, and disease duration. 722 MS patients with a mean (±SD age at enrollment of 41 (±10 years were followed for 44 (±28 months. The AD risk-associated allele of a non-synonymous SNP in the PCK1 locus (rs8192708G is associated with a smaller average brain volume (P=0.0047 at the baseline MRI, but it does not impact our baseline estimate of cognition. PCK1 is additionally associated with higher baseline T2-hyperintense lesion volume (P=0.0088. Finally, we provide technical validation of our observation in a subset of 641 subjects that have more than one MRI study, demonstrating the same association between PCK1 and smaller average brain volume (P=0.0089 at the last MRI visit.Our study provides suggestive evidence for greater brain atrophy in MS patients bearing the PCK1 allele associated with AD-susceptibility, yielding new insights into potentially shared neurodegenerative process between MS and late onset AD.

  1. Brain mitochondria as a primary target in the development of treatment strategies for Alzheimer disease.

    Science.gov (United States)

    Aliev, Gjumrakch; Palacios, Hector H; Walrafen, Brianna; Lipsitt, Amanda E; Obrenovich, Mark E; Morales, Ludis

    2009-10-01

    Alzheimer's disease (AD) and cerebrovascular accidents are two leading causes of age-related dementia. Increasing evidence supports the idea that chronic hypoperfusion is primarily responsible for the pathogenesis that underlies both disease processes. In this regard, hypoperfusion appears to induce oxidative stress (OS), which is largely due to reactive oxygen species (ROS), and over time initiates mitochondrial failure which is known as an initiating factor of AD. Recent evidence indicates that chronic injury stimulus induces hypoperfusion seen in vulnerable brain regions. This reduced regional cerebral blood flow (CBF) then leads to energy failure within the vascular endothelium and associated brain parenchyma, manifested by damaged mitochondrial ultrastructure (the formation of large number of immature, electron-dense "hypoxic" mitochondria) and by overproduction of mitochondrial DNA (mtDNA) deletions. Additionally, these mitochondrial abnormalities co-exist with increased redox metal activity, lipid peroxidation, and RNA oxidation. Interestingly, vulnerable neurons and glial cells show mtDNA deletions and oxidative stress markers only in the regions that are closely associated with damaged vessels, and, moreover, brain vascular wall lesions linearly correlate with the degree of neuronal and glial cell damage. We summarize the large body of evidence which indicates that sporadic, late-onset AD results from a vascular etiology by briefly reviewing mitochondrial damage and vascular risk factors associated with the disease and then we discuss the cerebral microvascular changes reason for the energy failure that occurs in normal aging and, to a much greater extent, AD.

  2. Cerebral hemodynamics of the aging brain: risk of Alzheimer disease and benefit of aerobic exercise

    Directory of Open Access Journals (Sweden)

    Takashi eTarumi

    2014-01-01

    Full Text Available Alzheimer disease (AD and cerebrovascular disease often coexist with advanced age. Mounting evidence indicates that the presence of vascular disease and its risk factors increase the risk of AD, suggesting a potential overlap of the underlying pathophysiological mechanisms. In particular, atherosclerosis, endothelial dysfunction, and stiffening of central elastic arteries have been shown to associate with AD. Currently, there are no effective treatments for the cure and prevention of AD. Vascular risk factors are modifiable via either pharmacological or lifestyle intervention. In this regard, habitual aerobic exercise is increasingly recognized for its benefits on brain structure and cognitive function. Considering the well-established benefits of regular aerobic exercise on vascular health, exercise-related improvements in brain structure and cognitive function may be mediated by vascular adaptations. In this review, we will present the current evidence for the physiological mechanisms by which vascular health alters the structural and functional integrity of the aging brain and how improvements in vascular health, via regular aerobic exercise, potentially benefits cognitive function.

  3. Cerebral hemodynamics of the aging brain: risk of Alzheimer disease and benefit of aerobic exercise.

    Science.gov (United States)

    Tarumi, Takashi; Zhang, Rong

    2014-01-01

    Alzheimer disease (AD) and cerebrovascular disease often coexist with advanced age. Mounting evidence indicates that the presence of vascular disease and its risk factors increase the risk of AD, suggesting a potential overlap of the underlying pathophysiological mechanisms. In particular, atherosclerosis, endothelial dysfunction, and stiffening of central elastic arteries have been shown to associate with AD. Currently, there are no effective treatments for the cure and prevention of AD. Vascular risk factors are modifiable via either pharmacological or lifestyle intervention. In this regard, habitual aerobic exercise is increasingly recognized for its benefits on brain structure and cognitive function. Considering the well-established benefits of regular aerobic exercise on vascular health, exercise-related improvements in brain structure and cognitive function may be mediated by vascular adaptations. In this review, we will present the current evidence for the physiological mechanisms by which vascular health alters the structural and functional integrity of the aging brain and how improvements in vascular health, via regular aerobic exercise, potentially benefits cognitive function.

  4. Association of Perivascular Localization of Aquaporin-4 With Cognition and Alzheimer Disease in Aging Brains.

    Science.gov (United States)

    Zeppenfeld, Douglas M; Simon, Matthew; Haswell, J Douglas; D'Abreo, Daryl; Murchison, Charles; Quinn, Joseph F; Grafe, Marjorie R; Woltjer, Randall L; Kaye, Jeffrey; Iliff, Jeffrey J

    2017-01-01

    Cognitive impairment and dementia, including Alzheimer disease (AD), are common within the aging population, yet the factors that render the aging brain vulnerable to these processes are unknown. Perivascular localization of aquaporin-4 (AQP4) facilitates the clearance of interstitial solutes, including amyloid-β, through the brainwide network of perivascular pathways termed the glymphatic system, which may be compromised in the aging brain. To determine whether alterations in AQP4 expression or loss of perivascular AQP4 localization are features of the aging human brain and to define their association with AD pathology. Expression of AQP4 was analyzed in postmortem frontal cortex of cognitively healthy and histopathologically confirmed individuals with AD by Western blot or immunofluorescence for AQP4, amyloid-β 1-42, and glial fibrillary acidic protein. Postmortem tissue and clinical data were provided by the Oregon Health and Science University Layton Aging and Alzheimer Disease Center and Oregon Brain Bank. Postmortem tissue from 79 individuals was evaluated, including cognitively intact "young" individuals aged younger than 60 years (range, 33-57 years), cognitively intact "aged" individuals aged older than 60 years (range, 61-96 years) with no known neurological disease, and individuals older than 60 years (range, 61-105 years) of age with a clinical history of AD confirmed by histopathological evaluation. Forty-eight patient samples (10 young, 20 aged, and 18 with AD) underwent histological analysis. Sixty patient samples underwent Western blot analysis (15 young, 24 aged, and 21 with AD). Expression of AQP4 protein, AQP4 immunoreactivity, and perivascular AQP4 localization in the frontal cortex were evaluated. Expression of AQP4 was associated with advancing age among all individuals (R2 = 0.17; P = .003). Perivascular AQP4 localization was significantly associated with AD status independent of age (OR, 11.7 per 10% increase in localization; z

  5. The Nuclear Receptor PPARγ as a Therapeutic Target for Cerebrovascular and Brain Dysfunction in Alzheimer's Disease

    Science.gov (United States)

    Nicolakakis, Nektaria; Hamel, Edith

    2010-01-01

    Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear transcription factors that regulate peripheral lipid and glucose metabolism. Three subtypes make up the PPAR family (α, γ, β/δ), and synthetic ligands for PPARα (fibrates) and PPARγ (Thiazolidinediones, TZDs) are currently prescribed for the respective management of dyslipidemia and type 2 diabetes. In contrast to the well characterized action of PPARs in the periphery, little was known about the presence or function of these receptors in the brain and cerebral vasculature until fairly recently. Indeed, research in the last decade has uncovered these receptors in most brain cell types, and has shown that their activation, particularly that of PPARγ, is implicated in normal brain and cerebrovascular physiology, and confers protection under pathological conditions. Notably, accumulating evidence has highlighted the therapeutic potential of PPARγ ligands in the treatment of brain disorders such as Alzheimer's disease (AD), leading to the testing of the TZDs pioglitazone and rosiglitazone in AD clinical trials. This review will focus on the benefits of PPARγ agonists for vascular, neuronal and glial networks, and assess the value of these compounds as future AD therapeutics in light of evidence from transgenic mouse models and recent clinical trials. PMID:20725514

  6. [Theoretic basis on the same therapeutic program for different degenerative brain diseases in terms of the Governor Vessel: Alzheimer's disease and Parkinson's disease].

    Science.gov (United States)

    Wu, Junyan; Wang, Jie; Zhang, Junlong

    2015-05-01

    Through the consultation of TCM ancient classical theory, the relationship of kidney essence, marrow and brain is analyzed. It is discovered that the degenerative brain diseases, represented by Alzheimer's disease (AD) and Parkinson's disease (PD) share the same etiological basis as "kidney essence deficiency and brain marrow emptiness" and have the mutual pathological outcomes as yang qi declining. The Governor Vessel gathers yang qi of the whole body and maintains the normal functional activity of zangfu organs in the human body through the storage, regulation and invigoration of yang qi. It is viewed that the theory of the Governor Vessel is applied to treat the different degenerative brain diseases, which provides the theoretic support and practice guide for the thought of TCM as the same therapeutic program for the different diseases. As a result, the degenerative brain diseases can be retarded and the approach is provided to the effective prevention and treatment of degenerative diseases in central nerve system:

  7. ERP-based detection of brain pathology in rat models for preclinical Alzheimer's disease

    Science.gov (United States)

    Nouriziabari, Seyed Berdia

    Early pathological features of Alzheimer's disease (AD) include the accumulation of hyperphosphorylated tau protein (HP-tau) in the entorhinal cortex and progressive loss of basal forebrain (BF) cholinergic neurons. These pathologies are known to remain asymptomatic for many years before AD is clinically diagnosed; however, they may induce aberrant brain processing which can be captured as an abnormality in event-related potentials (ERPs). Here, we examined cortical ERPs while a differential associative learning paradigm was applied to adult male rats with entorhinal HP-tau, pharmacological blockade of muscarinic acetylcholine receptors, or both conditions. Despite no impairment in differential associative and reversal learning, each pathological feature induced distinct abnormality in cortical ERPs to an extent that was sufficient for machine classifiers to accurately detect a specific type of pathology based on these ERP features. These results highlight a potential use of ERPs during differential associative learning as a biomarker for asymptomatic AD pathology.

  8. Physical Exercise and Brain Mitochondrial Fitness: The Possible Role Against Alzheimer's Disease.

    Science.gov (United States)

    Bernardo, T C; Marques-Aleixo, I; Beleza, J; Oliveira, P J; Ascensão, A; Magalhães, J

    2016-09-01

    Exercise is one of the most effective strategies to maintain a healthy body and mind, with particular beneficial effects of exercise on promoting brain plasticity, increasing cognition and reducing the risk of cognitive decline and dementia in later life. Moreover, the beneficial effects resulting from increased physical activity occur at different levels of cellular organization, mitochondria being preferential target organelles. The relevance of this review article relies on the need to integrate the current knowledge of proposed mechanisms, focus mitochondria, to explain the protective effects of exercise that might underlie neuroplasticity and seeks to synthesize these data in the context of exploring exercise as a feasible intervention to delay cognitive impairment associated with neurodegenerative conditions, particularly Alzheimer disease. © 2016 International Society of Neuropathology.

  9. Voxel-based comparison of whole brain gray matter of patients with mild Alzheimer's disease with normal aging volunteers

    International Nuclear Information System (INIS)

    Xie Sheng; Wu Hongkun; Xiao Jiangxi; Wang Yinhua; Jiang Xuexiang

    2006-01-01

    Objective: To detect gray matter abnormalities of whole brain in patients with mild Alzheimer's disease (AD) by voxel-based morphometry (VBM). Methods: Thirteen patients with mild Alzheimer's disease and sixteen normal aging volunteers underwent 3D SPGR scanning. For every subject, data was transferred to PC to be normalized, segmented and smoothed using SPM99. Non-dependent samples T-tests were conducted to compare gray matter' density voxel to voxel between the two groups. Results Significant reductions in gray matter density were found in the bilateral hippocampi and nucleus amygdalae, bilateral insulae, bilateral medial thalami, bilateral rectus gyri, right superior temporal gyms, right caudate nucleus, fight prefrontal lobe, right basal forebrain and portions of right occipital lobe. Conclusion: VBM reveals significant gray matter' reductions of numeral cortices in mild Alzheimer's disease. It can be a useful method to evaluate the anatomical changes in the progress of the disease. (authors)

  10. Voxel-based discriminant map classification on brain ventricles for Alzheimer's disease

    Science.gov (United States)

    Wang, Jingnan; de Haan, Gerard; Unay, Devrim; Soldea, Octavian; Ekin, Ahmet

    2009-02-01

    One major hallmark of the Alzheimer's disease (AD) is the loss of neurons in the brain. In many cases, medical experts use magnetic resonance imaging (MRI) to qualitatively measure the neuronal loss by the shrinkage or enlargement of the structures-of-interest. Brain ventricle is one of the popular choices. It is easily detectable in clinical MR images due to the high contrast of the cerebro-spinal fluid (CSF) with the rest of the parenchyma. Moreover, atrophy in any periventricular structure will directly lead to ventricle enlargement. For quantitative analysis, volume is the common choice. However, volume is a gross measure and it cannot capture the entire complexity of the anatomical shape. Since most existing shape descriptors are complex and difficult-to-reproduce, more straightforward and robust ways to extract ventricle shape features are preferred in the diagnosis. In this paper, a novel ventricle shape based classification method for Alzheimer's disease has been proposed. Training process is carried out to generate two probability maps for two training classes: healthy controls (HC) and AD patients. By subtracting the HC probability map from the AD probability map, we get a 3D ventricle discriminant map. Then a matching coefficient has been calculated between each training subject and the discriminant map. An adjustable cut-off point of the matching coefficients has been drawn for the two classes. Generally, the higher the cut-off point that has been drawn, the higher specificity can be achieved. However, it will result in relatively lower sensitivity and vice versa. The benchmarked results against volume based classification show that the area under the ROC curves for our proposed method is as high as 0.86 compared with only 0.71 for volume based classification method.

  11. Genetic Association of HLA Gene Variants with MRI Brain Structure in Alzheimer's Disease.

    Science.gov (United States)

    Wang, Zi-Xuan; Wan, Yu; Tan, Lin; Liu, Jinyuan; Wang, Hui-Fu; Sun, Fu-Rong; Tan, Meng-Shan; Tan, Chen-Chen; Jiang, Teng; Tan, Lan; Yu, Jin-Tai

    2017-07-01

    There is accumulating evidence that the human leukocyte antigen (HLA) gene variants are associated with Alzheimer's disease (AD). However, how they affect AD occurrence is still unknown. In this study, we firstly investigated the association of gene variants in HLA gene variants and brain structures on MRI in a large sample from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to explore the effects of HLA on AD pathogenesis. We selected hippocampus, hippocampus CA1 subregion, parahippocampus, posterior cingulate, precuneus, middle temporal, entorhinal cortex, and amygdala as regions of interest (ROIs). According to the previous association studies of HLA variants and AD, 12 SNPs in HLA were identified in the dataset following quality control measures. In total group analysis, our results showed that TNF-α SNPs at rs2534672 and rs2395488 were significantly positively associated with the volume of the left middle temporal lobe (rs2534672: P = 0.00035, Pc = 0.004; rs2395488: P = 0.0038, Pc = 0.023) at baseline. In the longitudinal study, HFE rs1800562 was remarkably correlated with the lower atrophy rate of right middle temporal lobe (P = 0.0003, Pc = 0.003) and RAGE rs2070600 was associated with the atrophy rate of right hippocampus substructure-CA1 over 2 years (P = 0.003, Pc = 0.035). Furthermore, we detected the above four associations in mild cognitive impairment (MCI) subgroup analysis, as well as the association of rs2534672 with the baseline volume of the left middle temporal lobe in normal cognition (NC) subgroup analysis. Our study provided preliminary evidences that HLA gene variants might participate in the structural alteration of AD associated brain regions, hence modulating the susceptibility of AD.

  12. Decreased Complexity in Alzheimer's Disease: Resting-State fMRI Evidence of Brain Entropy Mapping

    Directory of Open Access Journals (Sweden)

    Bin Wang

    2017-11-01

    Full Text Available Alzheimer's disease (AD is a frequently observed, irreversible brain function disorder among elderly individuals. Resting-state functional magnetic resonance imaging (rs-fMRI has been introduced as an alternative approach to assessing brain functional abnormalities in AD patients. However, alterations in the brain rs-fMRI signal complexities in mild cognitive impairment (MCI and AD patients remain unclear. Here, we described the novel application of permutation entropy (PE to investigate the abnormal complexity of rs-fMRI signals in MCI and AD patients. The rs-fMRI signals of 30 normal controls (NCs, 33 early MCI (EMCI, 32 late MCI (LMCI, and 29 AD patients were obtained from the Alzheimer's disease Neuroimaging Initiative (ADNI database. After preprocessing, whole-brain entropy maps of the four groups were extracted and subjected to Gaussian smoothing. We performed a one-way analysis of variance (ANOVA on the brain entropy maps of the four groups. The results after adjusting for age and sex differences together revealed that the patients with AD exhibited lower complexity than did the MCI and NC controls. We found five clusters that exhibited significant differences and were distributed primarily in the occipital, frontal, and temporal lobes. The average PE of the five clusters exhibited a decreasing trend from MCI to AD. The AD group exhibited the least complexity. Additionally, the average PE of the five clusters was significantly positively correlated with the Mini-Mental State Examination (MMSE scores and significantly negatively correlated with Functional Assessment Questionnaire (FAQ scores and global Clinical Dementia Rating (CDR scores in the patient groups. Significant correlations were also found between the PE and regional homogeneity (ReHo in the patient groups. These results indicated that declines in PE might be related to changes in regional functional homogeneity in AD. These findings suggested that complexity analyses using PE

  13. Cellular model studies of brain-mediated phototherapy on Alzheimer's disease

    Science.gov (United States)

    Zhu, Ling; Liu, Timon Cheng-Yi; Hu, Bina; Li, Xiao-Yun; Wang, Yong-Qing

    2008-12-01

    Alzheimer's disease (AD) is now the most common neurodegenerative disease. Despite approval of several drugs for AD, the disease continues to rob millions of their memories and their lives. We have studied the cellular models of brain-mediated phototherapy on AD, and the studies will be reviewed in this paper. Genetic studies have shown that dysfunction of amyloid β-protein (Aβ) or tau is sufficient to cause AD. Aβ or Aβ induced redox stress induced neuron apoptosis might be as a cellular model of AD. We found red light at 640+/-15 nm from light emitting diode array (RLED640) might inhibit Aβ 25-35 induced PC12 cell apoptosis, which is mediated by cyclic adenosine monophosphate, and it might inhibit hydrogen peroxide (H2O2) induced differentiated PC12 cell (dPC12) apoptosis, which is mediated by tyrosine hydroxylase. There is rhythm dysfunction in AD. We found low intensity 810 nm laser irradiation might rehabilitate TNF-alpha induced inhibition of clock gen expression of NIH 3T3 fibroblasts. Our studies provide a foundation for photobiomodulation on brain to rehabilitate AD.

  14. The hunt for brain Aβ oligomers by peripherally circulating multi-functional nanoparticles: Potential therapeutic approach for Alzheimer disease.

    Science.gov (United States)

    Mancini, Simona; Minniti, Stefania; Gregori, Maria; Sancini, Giulio; Cagnotto, Alfredo; Couraud, Pierre-Olivier; Ordóñez-Gutiérrez, Lara; Wandosell, Francisco; Salmona, Mario; Re, Francesca

    2016-01-01

    We previously showed the ability of liposomes bi-functionalized with phosphatidic acid and an ApoE-derived peptide (mApoE-PA-LIP) to reduce brain Aβ in transgenic Alzheimer mice. Herein we investigated the efficacy of mApoE-PA-LIP to withdraw Aβ peptide in different aggregation forms from the brain, using a transwell cellular model of the blood-brain barrier and APP/PS1 mice. The spontaneous efflux of Aβ oligomers (Aβo), but not of Aβ fibrils, from the 'brain' side of the transwell was strongly enhanced (5-fold) in presence of mApoE-PA-LIP in the 'blood' compartment. This effect is due to a withdrawal of Aβo exerted by peripheral mApoE-PA-LIP by sink effect, because, when present in the brain side, they did not act as Aβo carrier and limit the oligomer efflux. In vivo peripheral administration of mApoE-PA-LIP significantly increased the plasma Aβ level, suggesting that Aβ-binding particles exploiting the sink effect can be used as a therapeutic strategy for Alzheimer disease. From the Clinical Editor: Alzheimer disease (AD) at present is an incurable disease, which is thought to be caused by an accumulation of amyloid-β (Aβ) peptides in the brain. Many strategies in combating this disease have been focused on either the prevention or dissolving these peptides. In this article, the authors showed the ability of liposomes bi-functionalized with phosphatidic acid and with an ApoE- derived peptide to withdraw amyloid peptides from the brain. The data would help the future design of more novel treatment for Alzheimer disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. 7 Warning Signs of Alzheimer's | Alzheimer's disease | NIH MedlinePlus the Magazine

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    ... of this page please turn Javascript on. Feature: Alzheimer's Disease 7 Warning Signs of Alzheimer's Past Issues / Fall 2010 Table of Contents The ... Suncoast Gerontology Center, University of South Florida. How Alzheimer's Changes the Brain The only definite way to ...

  16. How Alzheimer's Changes the Brain

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  17. Brain alpha-amylase - a novel energy regulator important in Alzheimer disease?

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    Byman, Elin; Schultz, Nina; Huitinga, I.; Fex, Malin; Wennström, Malin

    2018-01-01

    Reduced glucose metabolism and formation of polyglucosan bodies (PGB) are, beside amyloid beta plaques and neurofibrillary tangles, well-known pathological findings associated with Alzheimer's disease (AD). Since both glucose availability and PGB are regulated by enzymatic degradation of glycogen,

  18. Brain Insulin Resistance and Deficiency as Therapeutic Targets in Alzheimer's Disease

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    de la Monte, Suzanne M

    2012-01-01

    Alzheimer's disease [AD] is the most common cause of dementia in North America. Despite 30+ years of intense investigation, the field lacks consensus regarding the etiology and pathogenesis of sporadic AD, and therefore we still do not know the best strategies for treating and preventing this debilitating and costly disease. However, growing evidence supports the concept that AD is fundamentally a metabolic disease with substantial and progressive derangements in brain glucose utilization and responsiveness to insulin and insulin-like growth factor [IGF] stimulation. Moreover, AD is now recognized to be heterogeneous in nature, and not solely the end-product of aberrantly processed, misfolded, and aggregated oligomeric amyloid-beta peptides and hyperphosphorylated tau. Other factors, including impairments in energy metabolism, increased oxidative stress, inflammation, insulin and IGF resistance, and insulin/IGF deficiency in the brain should be incorporated into all equations used to develop diagnostic and therapeutic approaches to AD. Herein, the contributions of impaired insulin and IGF signaling to AD-associated neuronal loss, synaptic disconnection, tau hyperphosphorylation, amyloid-beta accumulation, and impaired energy metabolism are reviewed. In addition, we discuss current therapeutic strategies and suggest additional approaches based on the hypothesis that AD is principally a metabolic disease similar to diabetes mellitus. Ultimately, our ability to effectively detect, monitor, treat, and prevent AD will require more efficient, accurate and integrative diagnostic tools that utilize clinical, neuroimaging, biochemical, and molecular biomarker data. Finally, it is imperative that future therapeutic strategies for AD abandon the concept of uni-modal therapy in favor of multi-modal treatments that target distinct impairments at different levels within the brain insulin/IGF signaling cascades. PMID:22329651

  19. Changes in brain oxysterols at different stages of Alzheimer's disease: Their involvement in neuroinflammation

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    Gabriella Testa

    2016-12-01

    Full Text Available Alzheimer's disease (AD is a gradually debilitating disease that leads to dementia. The molecular mechanisms underlying AD are still not clear, and at present no reliable biomarkers are available for the early diagnosis. In the last several years, together with oxidative stress and neuroinflammation, altered cholesterol metabolism in the brain has become increasingly implicated in AD progression. A significant body of evidence indicates that oxidized cholesterol, in the form of oxysterols, is one of the main triggers of AD. The oxysterols potentially most closely involved in the pathogenesis of AD are 24-hydroxycholesterol and 27-hydroxycholesterol, respectively deriving from cholesterol oxidation by the enzymes CYP46A1 and CYP27A1. However, the possible involvement of oxysterols resulting from cholesterol autooxidation, including 7-ketocholesterol and 7β-hydroxycholesterol, is now emerging. In a systematic analysis of oxysterols in post-mortem human AD brains, classified by the Braak staging system of neurofibrillary pathology, alongside the two oxysterols of enzymatic origin, a variety of oxysterols deriving from cholesterol autoxidation were identified; these included 7-ketocholesterol, 7α-hydroxycholesterol, 4β-hydroxycholesterol, 5α,6α-epoxycholesterol, and 5β,6β-epoxycholesterol. Their levels were quantified and compared across the disease stages. Some inflammatory mediators, and the proteolytic enzyme matrix metalloprotease-9, were also found to be enhanced in the brains, depending on disease progression. This highlights the pathogenic association between the trends of inflammatory molecules and oxysterol levels during the evolution of AD. Conversely, sirtuin 1, an enzyme that regulates several pathways involved in the anti-inflammatory response, was reduced markedly with the progression of AD, supporting the hypothesis that the loss of sirtuin 1 might play a key role in AD. Taken together, these results strongly support the

  20. How Alzheimer's Changes the Brain

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    Full Text Available ... Get YouTube Red. Working... Not now Try it free Find out why Close How Alzheimer's Changes the ... 4:22 Your Amazing Brain - Dementia Explained - Alzheimer's Research UK - Duration: 4:58. AlzheimersResearch UK 16,695 ...

  1. Comparative Lipidomic Analysis of Mouse and Human Brain with Alzheimer Disease*

    Science.gov (United States)

    Chan, Robin B.; Oliveira, Tiago G.; Cortes, Etty P.; Honig, Lawrence S.; Duff, Karen E.; Small, Scott A.; Wenk, Markus R.; Shui, Guanghou; Di Paolo, Gilbert

    2012-01-01

    Lipids are key regulators of brain function and have been increasingly implicated in neurodegenerative disorders including Alzheimer disease (AD). Here, a systems-based approach was employed to determine the lipidome of brain tissues affected by AD. Specifically, we used liquid chromatography-mass spectrometry to profile extracts from the prefrontal cortex, entorhinal cortex, and cerebellum of late-onset AD (LOAD) patients, as well as the forebrain of three transgenic familial AD (FAD) mouse models. Although the cerebellum lacked major alterations in lipid composition, we found an elevation of a signaling pool of diacylglycerol as well as sphingolipids in the prefrontal cortex of AD patients. Furthermore, the diseased entorhinal cortex showed specific enrichment of lysobisphosphatidic acid, sphingomyelin, the ganglioside GM3, and cholesterol esters, all of which suggest common pathogenic mechanisms associated with endolysosomal storage disorders. Importantly, a significant increase in cholesterol esters and GM3 was recapitulated in the transgenic FAD models, suggesting that these mice are relevant tools to study aberrant lipid metabolism of endolysosomal dysfunction associated with AD. Finally, genetic ablation of phospholipase D2, which rescues the synaptic and behavioral deficits of an FAD mouse model, fully normalizes GM3 levels. These data thus unmask a cross-talk between the metabolism of phosphatidic acid, the product of phospholipase D2, and gangliosides, and point to a central role of ganglioside anomalies in AD pathogenesis. Overall, our study highlights the hypothesis generating potential of lipidomics and identifies novel region-specific lipid anomalies potentially linked to AD pathogenesis. PMID:22134919

  2. The classification of microglial activation phenotypes on neurodegeneration and regeneration in Alzheimer's disease brain.

    Science.gov (United States)

    Varnum, Megan M; Ikezu, Tsuneya

    2012-08-01

    Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive decline of cognitive function. There is no therapy that can halt or reverse its progression. Contemporary research suggests that age-dependent neuroinflammatory changes may play a significant role in the decreased neurogenesis and cognitive impairments in AD. The innate immune response is characterized by pro-inflammatory (M1) activation of macrophages and subsequent production of specific cytokines, chemokines, and reactive intermediates, followed by resolution and alternative activation for anti-inflammatory signaling (M2a) and wound healing (M2c). We propose that microglial activation phenotypes are analogous to those of macrophages and that their activation plays a significant role in regulating neurogenesis in the brain. Microglia undergo a switch from an M2- to an M1-skewed activation phenotype during aging. This review will assess the neuroimmunological studies that led to characterization of the different microglial activation states in AD mouse models. It will also discuss the roles of microglial activation on neurogenesis in AD and propose anti-inflammatory molecules as exciting therapeutic targets for research. Molecules such as interleukin-4 and CD200 have proven to be important anti-inflammatory mediators in the regulation of neuroinflammation in the brain, which will be discussed in detail for their therapeutic potential.

  3. Brain Aging and Late-Onset Alzheimer's Disease: A Matter of Increased Amyloid or Reduced Energy?

    Science.gov (United States)

    Mecocci, Patrizia; Baroni, Marta; Senin, Umberto; Boccardi, Virginia

    2018-03-16

    Alzheimer's disease (AD) represents the most common form of dementia in old age subjects, and despite decades of studies, the underlying etiopathogenetic mechanisms remain unsolved. The definition of AD has changed over the past years, offering an ever more detailed definition of pre-morbid and pre-clinical status, but without a similar strong emphasis on the role of aging as the main risk factor. In fact, while early-onset AD is a clear consequence of gene mutations, late-onset AD is more likely due to a gradual accumulation of age-related damages. The pathogenetic amyloid cascade hypothesis has been recently questioned due to multiple clinical failures. Furthermore, several studies reported that cognitively normal elderly have a high amyloid deposition in the brain comparable to the levels observed in old age subjects with AD. This suggests that amyloid accumulation enters into the normal process of aging and what really triggers neuronal death and clinical manifestation in late-onset AD still needs further explanation. In this context, 'normal brain aging' and AD might represent a different pathway of successful or failed capability to adapt brain structures and cerebral functions. Cellular senescence and age-related changes affecting the brain may be considered as biologic manifestations of increasing entropy. Bioenergetic deficits due to mitochondrial dysfunction may lead to progressive neuronal death and clinical expression of dementia. So, increased amyloid in the brain of old age subjects may represent the downstream event expression of a biological system that is cooling down because of its exhaustion and not the core causative factor of late-onset dementia.

  4. Multifactorial causal model of brain (dis)organization and therapeutic intervention: Application to Alzheimer's disease.

    Science.gov (United States)

    Iturria-Medina, Yasser; Carbonell, Félix M; Sotero, Roberto C; Chouinard-Decorte, Francois; Evans, Alan C

    2017-05-15

    Generative models focused on multifactorial causal mechanisms in brain disorders are scarce and generally based on limited data. Despite the biological importance of the multiple interacting processes, their effects remain poorly characterized from an integrative analytic perspective. Here, we propose a spatiotemporal multifactorial causal model (MCM) of brain (dis)organization and therapeutic intervention that accounts for local causal interactions, effects propagation via physical brain networks, cognitive alterations, and identification of optimum therapeutic interventions. In this article, we focus on describing the model and applying it at the population-based level for studying late onset Alzheimer's disease (LOAD). By interrelating six different neuroimaging modalities and cognitive measurements, this model accurately predicts spatiotemporal alterations in brain amyloid-β (Aβ) burden, glucose metabolism, vascular flow, resting state functional activity, structural properties, and cognitive integrity. The results suggest that a vascular dysregulation may be the most-likely initial pathologic event leading to LOAD. Nevertheless, they also suggest that LOAD it is not caused by a unique dominant biological factor (e.g. vascular or Aβ) but by the complex interplay among multiple relevant direct interactions. Furthermore, using theoretical control analysis of the identified population-based multifactorial causal network, we show the crucial advantage of using combinatorial over single-target treatments, explain why one-target Aβ based therapies might fail to improve clinical outcomes, and propose an efficiency ranking of possible LOAD interventions. Although still requiring further validation at the individual level, this work presents the first analytic framework for dynamic multifactorial brain (dis)organization that may explain both the pathologic evolution of progressive neurological disorders and operationalize the influence of multiple interventional

  5. Accelerated Brain Atrophy on Serial Computed Tomography: Potential Marker of the Progression of Alzheimer Disease.

    Science.gov (United States)

    Bin Zahid, Abdullah; Mikheev, Artem; Srivatsa, Neha; Babb, James; Samadani, Uzma; Rusinek, Henry

    2016-01-01

    The aim of this study was to validate computed tomography (CT)-based longitudinal markers of the progression of Alzheimer disease (AD). We retrospectively studied 33 AD patients and 39 nondemented patients with other neurological illnesses (non-AD) having 4 to 12 CT examinations of the head, with over a mean (SD) of 3.9 (1.7) years. At each time point, we applied an automatic software to measure whole brain, cerebrospinal fluid, and intracranial space volumes. Longitudinal measures were then related to disease status and time since the first scan using hierarchical models. Absolute brain volume loss accelerated for non-AD patients by 0.86 mL/y (95% confidence interval [CI], 0.64-1.08 mL/y) and 1.5× faster, that is, 1.32 mL/y (95% CI, 1.09-1.56 mL/y) for AD patients (P = 0.006). In terms of brain volume normalized to intracranial space, the acceleration in atrophy rate for non-AD patients was 0.0578%/y (95% CI, 0.0389%/y to 0.0767%/y), again 1.5× faster, that is, 0.0919%/y (95% CI, 0.0716%/y to 0.1122%/y) for AD patients (P = 0.017). This translates to an increase in atrophy rate from 0.5% to 1.4% in AD versus to 1.1% in non-AD group after 10 years. Brain volumetry on CT reliably detected accelerated volume loss in AD and significantly lower acceleration factor in age-matched non-AD patients, leading to the possibility of its use to monitor the progression of cognitive decline and dementia.

  6. Neurogenesis and Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Philippe Taupin

    2006-01-01

    Full Text Available Alzheimer's disease (AD is a neurodegenerative disease, characterized in the brain by amyloid plaque deposits and neurofibrillary tangles. It is the most common form of dementia among older people. There is at present no cure for AD, and current treatments consist mainly in drug therapy. Potential therapies for AD involve gene and cellular therapy. The recent confirmation that neurogenesis occurs in the adult brain and neural stem cells (NSCs reside in the adult central nervous system (CNS provide new opportunities for cellular therapy in the CNS, particularly for AD, and to better understand brain physiopathology. Hence, researchers have aimed at characterizing neurogenesis in patients with AD. Studies show that neurogenesis is increased in these patients, and in animal models of AD. The effect of drugs used to treat AD on neurogenesis is currently being investigated, to identify whether neurogenesis contributes to their therapeutic activities.

  7. Identification of Differentially Expressed Genes through Integrated Study of Alzheimer's Disease Affected Brain Regions.

    Directory of Open Access Journals (Sweden)

    Nisha Puthiyedth

    Full Text Available Alzheimer's disease (AD is the most common form of dementia in older adults that damages the brain and results in impaired memory, thinking and behaviour. The identification of differentially expressed genes and related pathways among affected brain regions can provide more information on the mechanisms of AD. In the past decade, several studies have reported many genes that are associated with AD. This wealth of information has become difficult to follow and interpret as most of the results are conflicting. In that case, it is worth doing an integrated study of multiple datasets that helps to increase the total number of samples and the statistical power in detecting biomarkers. In this study, we present an integrated analysis of five different brain region datasets and introduce new genes that warrant further investigation.The aim of our study is to apply a novel combinatorial optimisation based meta-analysis approach to identify differentially expressed genes that are associated to AD across brain regions. In this study, microarray gene expression data from 161 samples (74 non-demented controls, 87 AD from the Entorhinal Cortex (EC, Hippocampus (HIP, Middle temporal gyrus (MTG, Posterior cingulate cortex (PC, Superior frontal gyrus (SFG and visual cortex (VCX brain regions were integrated and analysed using our method. The results are then compared to two popular meta-analysis methods, RankProd and GeneMeta, and to what can be obtained by analysing the individual datasets.We find genes related with AD that are consistent with existing studies, and new candidate genes not previously related with AD. Our study confirms the up-regualtion of INFAR2 and PTMA along with the down regulation of GPHN, RAB2A, PSMD14 and FGF. Novel genes PSMB2, WNK1, RPL15, SEMA4C, RWDD2A and LARGE are found to be differentially expressed across all brain regions. Further investigation on these genes may provide new insights into the development of AD. In addition, we

  8. Brain and blood metabolite signatures of pathology and progression in Alzheimer disease: A targeted metabolomics study.

    Directory of Open Access Journals (Sweden)

    Vijay R Varma

    2018-01-01

    Full Text Available The metabolic basis of Alzheimer disease (AD is poorly understood, and the relationships between systemic abnormalities in metabolism and AD pathogenesis are unclear. Understanding how global perturbations in metabolism are related to severity of AD neuropathology and the eventual expression of AD symptoms in at-risk individuals is critical to developing effective disease-modifying treatments. In this study, we undertook parallel metabolomics analyses in both the brain and blood to identify systemic correlates of neuropathology and their associations with prodromal and preclinical measures of AD progression.Quantitative and targeted metabolomics (Biocrates AbsoluteIDQ [identification and quantification] p180 assays were performed on brain tissue samples from the autopsy cohort of the Baltimore Longitudinal Study of Aging (BLSA (N = 44, mean age = 81.33, % female = 36.36 from AD (N = 15, control (CN; N = 14, and "asymptomatic Alzheimer's disease" (ASYMAD, i.e., individuals with significant AD pathology but no cognitive impairment during life; N = 15 participants. Using machine-learning methods, we identified a panel of 26 metabolites from two main classes-sphingolipids and glycerophospholipids-that discriminated AD and CN samples with accuracy, sensitivity, and specificity of 83.33%, 86.67%, and 80%, respectively. We then assayed these 26 metabolites in serum samples from two well-characterized longitudinal cohorts representing prodromal (Alzheimer's Disease Neuroimaging Initiative [ADNI], N = 767, mean age = 75.19, % female = 42.63 and preclinical (BLSA (N = 207, mean age = 78.68, % female = 42.63 AD, in which we tested their associations with magnetic resonance imaging (MRI measures of AD-related brain atrophy, cerebrospinal fluid (CSF biomarkers of AD pathology, risk of conversion to incident AD, and trajectories of cognitive performance. We developed an integrated blood and brain endophenotype score that summarized the relative importance of

  9. How Alzheimer's Changes the Brain

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    Full Text Available ... Find out why Close How Alzheimer's Changes the Brain National Institute On Aging Loading... Unsubscribe from National ... minute video shows how Alzheimer’s affects the human brain and looks at promising ideas to treat and ...

  10. How Alzheimer's Changes the Brain

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    Full Text Available ... Queue __count__/__total__ Find out why Close How Alzheimer's Changes the Brain National Institute On Aging Loading... ... 23, 2017 This 4-minute video shows how Alzheimer’s affects the human brain and looks at promising ...

  11. How Alzheimer's Changes the Brain

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    Full Text Available ... Queue Queue __count__/__total__ Find out why Close How Alzheimer's Changes the Brain National Institute On Aging ... Aug 23, 2017 This 4-minute video shows how Alzheimer’s affects the human brain and looks at ...

  12. How Alzheimer's Changes the Brain

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    ... Try it free Find out why Close How Alzheimer's Changes the Brain National Institute On Aging Loading... ... 23, 2017 This 4-minute video shows how Alzheimer’s affects the human brain and looks at promising ...

  13. How Alzheimer's Changes the Brain

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    Full Text Available ... Try it free Find out why Close How Alzheimer's Changes the Brain National Institute On Aging Loading... ... 23, 2017 This 4-minute video shows how Alzheimer’s affects the human brain and looks at promising ...

  14. FLOW-BASED NETWORK MEASURES OF BRAIN CONNECTIVITY IN ALZHEIMER'S DISEASE.

    Science.gov (United States)

    Prasad, Gautam; Joshi, Shantanu H; Nir, Talia M; Toga, Arthur W; Thompson, Paul M

    2013-01-01

    We present a new flow-based method for modeling brain structural connectivity. The method uses a modified maximum-flow algorithm that is robust to noise in the diffusion data and guided by biologically viable pathways and structure of the brain. A flow network is first created using a lattice graph by connecting all lattice points (voxel centers) to all their neighbors by edges. Edge weights are based on the orientation distribution function (ODF) value in the direction of the edge. The maximum-flow is computed based on this flow graph using the flow or the capacity between each region of interest (ROI) pair by following the connected tractography fibers projected onto the flow graph edges. Network measures such as global efficiency, transitivity, path length, mean degree, density, modularity, small world, and assortativity are computed from the flow connectivity matrix. We applied our method to diffusion-weighted images (DWIs) from 110 subjects (28 normal elderly, 56 with early and 11 with late mild cognitive impairment, and 15 with AD) and segmented co-registered anatomical MRIs into cortical regions. Experimental results showed better performance compared to the standard fiber-counting methods when distinguishing Alzheimer's disease from normal aging.

  15. Elevated stearoyl-CoA desaturase in brains of patients with Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Giuseppe Astarita

    Full Text Available The molecular bases of Alzheimer's disease (AD remain unclear. We used a lipidomic approach to identify lipid abnormalities in the brains of subjects with AD (N = 37 compared to age-matched controls (N = 17. The analyses revealed statistically detectable elevations in levels of non-esterified monounsaturated fatty acids (MUFAs and mead acid (20:3n-9 in mid-frontal cortex, temporal cortex and hippocampus of AD patients. Further studies showed that brain mRNAs encoding for isoforms of the rate-limiting enzyme in MUFAs biosynthesis, stearoyl-CoA desaturase (SCD-1, SCD-5a and SCD-5b, were elevated in subjects with AD. The monounsaturated/saturated fatty acid ratio ('desaturation index'--displayed a strong negative correlation with measures of cognition: the Mini Mental State Examination test (r = -0.80; P = 0.0001 and the Boston Naming test (r = -0.57; P = 0.0071. Our results reveal a previously unrecognized role for the lipogenic enzyme SCD in AD.

  16. Blood-Brain Barrier Leakage in Patients with Early Alzheimer Disease.

    Science.gov (United States)

    van de Haar, Harm J; Burgmans, Saartje; Jansen, Jacobus F A; van Osch, Matthias J P; van Buchem, Mark A; Muller, Majon; Hofman, Paul A M; Verhey, Frans R J; Backes, Walter H

    2016-11-01

    Purpose To investigate whether the blood-brain barrier (BBB) leaks blood-circulating substances in patients with early forms of Alzheimer disease (AD), and if so, to examine the extent and pattern of leakage. Materials and Methods This study was approved by the local medical ethical committees of the Maastricht University Medical Center and Leiden University Medical Center, and written informed consent was obtained from all subjects. For this pilot study, 16 patients with early AD and 17 healthy age-matched control subjects underwent dynamic contrast material-enhanced magnetic resonance (MR) imaging sequence with dual time resolution for 25 minutes. The Patlak graphical approach was used to quantify the BBB leakage rate and local blood plasma volume. Subsequent histogram analysis was used to determine the volume fraction of the leaking brain tissue. Differences were assessed with linear regression analysis, adjusted for confounding variables. Results The BBB leakage rate was significantly higher in patients compared with that in control subjects in the total gray matter (P cascade of pathologic events that eventually lead to cognitive decline and dementia. © RSNA, 2016 Online supplemental material is available for this article.

  17. Morphological and pathological evolution of the brain microcirculation in aging and Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Jesse M Hunter

    Full Text Available Key pathological hallmarks of Alzheimer's disease (AD, including amyloid plaques, cerebral amyloid angiopathy (CAA and neurofibrillary tangles do not completely account for cognitive impairment, therefore other factors such as cardiovascular and cerebrovascular pathologies, may contribute to AD. In order to elucidate the microvascular changes that contribute to aging and disease, direct neuropathological staining and immunohistochemistry, were used to quantify the structural integrity of the microvasculature and its innervation in three oldest-old cohorts: 1 nonagenarians with AD and a high amyloid plaque load; 2 nonagenarians with no dementia and a high amyloid plaque load; 3 nonagenarians without dementia or amyloid plaques. In addition, a non-demented (ND group (average age 71 years with no amyloid plaques was included for comparison. While gray matter thickness and overall brain mass were reduced in AD compared to ND control groups, overall capillary density was not different. However, degenerated string capillaries were elevated in AD, potentially suggesting greater microvascular "dysfunction" compared to ND groups. Intriguingly, apolipoprotein ε4 carriers had significantly higher string vessel counts relative to non-ε4 carriers. Taken together, these data suggest a concomitant loss of functional capillaries and brain volume in AD subjects. We also demonstrated a trend of decreasing vesicular acetylcholine transporter staining, a marker of cortical cholinergic afferents that contribute to arteriolar vasoregulation, in AD compared to ND control groups, suggesting impaired control of vasodilation in AD subjects. In addition, tyrosine hydroxylase, a marker of noradrenergic vascular innervation, was reduced which may also contribute to a loss of control of vasoconstriction. The data highlight the importance of the brain microcirculation in the pathogenesis and evolution of AD.

  18. Effect of aging and Alzheimer's disease-like pathology on brain monoamines in mice.

    Science.gov (United States)

    Von Linstow, C U; Severino, M; Metaxas, A; Waider, J; Babcock, A A; Lesch, K P; Gramsbergen, J B; Finsen, B

    2017-09-01

    Aging is the greatest single risk factor of the neurodegenerative disorder Alzheimer's disease (AD). The monoaminergic system, including serotonin (5-HT), dopamine (DA) and noradrenaline (NA) modulates cognition, which is affected in AD. Changes in monoamine levels have been observed in AD, but these can both be age- and/or disease-related. We examined whether brain monoamine levels change as part of physiological aging and/or AD-like disease in APP SWE /PS1 ΔE9 (APP/PS1) transgenic mice. The neocortex, hippocampus, striatum, brainstem and cerebellum of 6-, 12-, 18- and 24-month-old B6C3 wild-type (WT) mice and of 18-month old APP/PS1 and WT mice were analysed for 5-HT, DA and NA contents by high pressure liquid chromatography (HPLC), along with neocortex from 14-month-old APP/PS1 and WT mice. While, we observed no aging effect in WT mice, we detected region-specific changes in the levels of all monoamines in 18-month-old transgenic compared with WT mice. This included reductions in 5-HT (-30%), DA (-47%) and NA (-32%) levels in the neocortex and increases of 5-HT in the brainstem (+18%). No changes were observed in any of the monoamines in the neocortex from 14-month-old APP/PS1 mice. In combination, these findings indicate that aging alone is not sufficient to affect brain monoamine levels, unlike the APP SWE /PS1 ΔE9 genotype. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. [Proceeding memory in Alzheimer's disease].

    Science.gov (United States)

    Arroyo-Anlló, Eva Ma; Chamorro-Sánchez, Jorge; Díaz-Marta, Juan Poveda; Gil, Roger

    2013-01-01

    Procedural learning can acquire or develop skills through performance and repetition of a task unconsciously or unintentionally. Procedural skills are considered as the cornerstone in the neuropsychological rehabilitation to promote the autonomy of patients with brain damage, as those with Alzheimer's disease. This review presents data about procedural skills in Alzheimer's disease. Over the past three decades, we have found 40 articles studying various procedural skills in the Alzheimer's disease: motor, perceptual-motor, cognitive, perceptual-cognitive and those developed through serial reaction-time paradigm. We analyzed every study evaluating a procedural skill, indicating the used task and preservation or no preservation of procedural learning. Overall, most of the papers published describe conservation of learning procedures or relatively conserved in Alzheimer's disease, which could be used to promote patient autonomy.

  20. Brain imaging and cognitive predictors of stroke and Alzheimer disease in the Framingham Heart Study.

    Science.gov (United States)

    Weinstein, Galit; Beiser, Alexa S; Decarli, Charles; Au, Rhoda; Wolf, Philip A; Seshadri, Sudha

    2013-10-01

    Exposure to vascular risk factors has a gradual deleterious effect on brain MRI and cognitive measures. We explored whether a pattern of these measures exists that predicts stroke and Alzheimer disease (AD) risk. A cognitive battery was administered to 1679 dementia and stroke-free Framingham offspring (age, >55 years; mean, 65.7±7.0) between 1999 and 2004; participants were also free of other neurological conditions that could affect cognition and >90% also had brain MRI examination. We related cognitive and MRI measures to risks of incident stroke and AD ≤10 years of follow-up. As a secondary analysis, we explored these associations in The Framingham Heart Study original cohort (mean age, 67.5±7.3 and 84.8±3.3 years at the cognitive assessment and MRI examination, respectively). A total of 55 Offspring participants sustained strokes and 31 developed AD. Offspring who scored stroke (hazard ratio [HR], 2.27; 95% confidence interval [CI], 1.06-4.85) and AD (HR, 3.60; 95% CI, 1.52-8.52); additional cognitive tests also predicted AD. Participants with low (20 percentile) white matter hyperintensity volume had a higher risk of stroke (HR, 1.97; 95% CI, 1.03-3.77 and HR, 2.74; 95% CI, 1.51-5.00, respectively) but not AD. Hippocampal volume at the bottom quintile predicted AD in the offspring and original cohorts (HR, 4.41; 95% CI, 2.00-9.72 and HR, 2.37; 95% CI, 1.12-5.00, respectively). A stepwise increase in stroke risk was apparent with increasing numbers of these cognitive and imaging markers. Specific patterns of cognitive and brain structural measures observed even in early aging predict stroke risk and may serve as biomarkers for risk prediction.

  1. A Phase II Study of Fornix Deep Brain Stimulation in Mild Alzheimer's Disease.

    Science.gov (United States)

    Lozano, Andres M; Fosdick, Lisa; Chakravarty, M Mallar; Leoutsakos, Jeannie-Marie; Munro, Cynthia; Oh, Esther; Drake, Kristen E; Lyman, Christopher H; Rosenberg, Paul B; Anderson, William S; Tang-Wai, David F; Pendergrass, Jo Cara; Salloway, Stephen; Asaad, Wael F; Ponce, Francisco A; Burke, Anna; Sabbagh, Marwan; Wolk, David A; Baltuch, Gordon; Okun, Michael S; Foote, Kelly D; McAndrews, Mary Pat; Giacobbe, Peter; Targum, Steven D; Lyketsos, Constantine G; Smith, Gwenn S

    2016-09-06

    Deep brain stimulation (DBS) is used to modulate the activity of dysfunctional brain circuits. The safety and efficacy of DBS in dementia is unknown. To assess DBS of memory circuits as a treatment for patients with mild Alzheimer's disease (AD). We evaluated active "on" versus sham "off" bilateral DBS directed at the fornix-a major fiber bundle in the brain's memory circuit-in a randomized, double-blind trial (ClinicalTrials.gov NCT01608061) in 42 patients with mild AD. We measured cognitive function and cerebral glucose metabolism up to 12 months post-implantation. Surgery and electrical stimulation were safe and well tolerated. There were no significant differences in the primary cognitive outcomes (ADAS-Cog 13, CDR-SB) in the "on" versus "off" stimulation group at 12 months for the whole cohort. Patients receiving stimulation showed increased metabolism at 6 months but this was not significant at 12 months. On post-hoc analysis, there was a significant interaction between age and treatment outcome: in contrast to patients <65 years old (n = 12) whose results trended toward being worse with DBS ON versus OFF, in patients≥65 (n = 30) DBS-f ON treatment was associated with a trend toward both benefit on clinical outcomes and a greater increase in cerebral glucose metabolism. DBS for AD was safe and associated with increased cerebral glucose metabolism. There were no differences in cognitive outcomes for participants as a whole, but participants aged≥65 years may have derived benefit while there was possible worsening in patients below age 65 years with stimulation.

  2. Who fans the flames of Alzheimer's disease brains? Misfolded tau on the crossroad of neurodegenerative and inflammatory pathways.

    Science.gov (United States)

    Zilka, Norbert; Kazmerova, Zuzana; Jadhav, Santosh; Neradil, Peter; Madari, Aladar; Obetkova, Dominika; Bugos, Ondrej; Novak, Michal

    2012-03-07

    Neurodegeneration, induced by misfolded tau protein, and neuroinflammation, driven by glial cells, represent the salient features of Alzheimer's disease (AD) and related human tauopathies. While tau neurodegeneration significantly correlates with disease progression, brain inflammation seems to be an important factor in regulating the resistance or susceptibility to AD neurodegeneration. Previously, it has been shown that there is a reciprocal relationship between the local inflammatory response and neurofibrillary lesions. Numerous independent studies have reported that inflammatory responses may contribute to the development of tau pathology and thus accelerate the course of disease. It has been shown that various cytokines can significantly affect the functional and structural properties of intracellular tau. Notwithstanding, anti-inflammatory approaches have not unequivocally demonstrated that inhibition of the brain immune response can lead to reduction of neurofibrillary lesions. On the other hand, our recent data show that misfolded tau could represent a trigger for microglial activation, suggesting the dual role of misfolded tau in the Alzheimer's disease inflammatory cascade. On the basis of current knowledge, we can conclude that misfolded tau is located at the crossroad of the neurodegenerative and neuroinflammatory pathways. Thus disease-modified tau represents an important target for potential therapeutic strategies for patients with Alzheimer's disease.

  3. Brain-Derived Neurotrophic Factor Serum Levels and Hippocampal Volume in Mild Cognitive Impairment and Dementia due to Alzheimer Disease

    OpenAIRE

    Borba, Ericksen Mielle; Duarte, Juliana Avila; Bristot, Giovana; Scotton, Ellen; Camozzato, Ana Luiza; Chaves, M?rcia Lorena Fagundes

    2016-01-01

    Background/Aims: Hippocampal atrophy is a recognized biomarker of Alzheimer disease (AD) pathology. Serum brain-derived neurotrophic factor (BDNF) reduction has been associated with neurodegeneration. We aimed to evaluate BDNF serum levels and hippocampal volume in clinical AD (dementia and mild cognitive impairment [MCI]). Methods: Participants were 10 patients with MCI and 13 with dementia due to AD as well as 10 healthy controls. BDNF serum levels were determined by ELISA and volumetric me...

  4. Clinical Evaluation of Brain Perfusion SPECT with Brodmann Areas Mapping in Early Diagnosis of Alzheimer's Disease.

    Science.gov (United States)

    Valotassiou, Varvara; Papatriantafyllou, John; Sifakis, Nikolaos; Tzavara, Chara; Tsougos, Ioannis; Psimadas, Dimitrios; Fezoulidis, Ioannis; Kapsalaki, Eftychia; Hadjigeorgiou, George; Georgoulias, Panagiotis

    2015-01-01

    Early diagnosis of Alzheimer's disease (AD) based on clinical criteria alone may be problematic, while current and future treatments should be administered earlier in order to be more effective. Thus, various disease biomarkers could be used for early detection of AD. We evaluated brain perfusion with 99mTc-HMPAO single photon emission computed tomography (SPECT) and Brodmann areas (BAs) mapping in mild AD using an automated software (NeuroGam) for the semi-quantitative evaluation of perfusion in BAs and the comparison with the software's normal database. We studied 34 consecutive patients with mild AD: 9 men, 25 women, mean age 70.9 ± 8.1 years, mean Mini-Mental State Examination 22.6 ± 2.5. BAs 25L, 25R, 38L, 38R, 28L, 28R, 36L, and 36R had the lower mean perfusion values, while BAs 31L, 31R, 19R, 18L, 18R, 17L, and 17R had the higher mean values. Compared with healthy subjects of the same age, perfusion values in BAs 25L, 25R, 28R, 28L, 36L, and 36R had the greatest deviations from the healthy sample, while the lowest deviations were found in BAs 32L, 32R, 19R, 24L, 17L, 17R, 18L, and 18R. A percentage of ≥94% of patients had perfusion values more than -2SDs below the mean of healthy subjects in BAs 38R, 38L, 36L, 36R, 23L, 23R, 22L, 44L, 28L, 28R, 25L, and 25R. The corresponding proportion was less than 38% for BAs 11L, 19R, 32L, 32R, 18L, 18R, 24L, and 17R. In conclusion, brain SPECT studies with automated perfusion mapping could be useful as an ancillary tool in daily practice, revealing perfusion impairments in early AD.

  5. Alzheimer's disease and amyloid beta-peptide deposition in the brain: a matter of 'aging'?

    Science.gov (United States)

    Moro, Maria Luisa; Collins, Matthew J; Cappellini, Enrico

    2010-04-01

    Biomolecules can experience aging processes that limit their long-term functionality in organisms. Typical markers of protein aging are spontaneous chemical modifications, such as AAR (amino acid racemization) and AAI (amino acid isomerization), mainly involving aspartate and asparagine residues. Since these modifications may affect folding and turnover, they reduce protein functionality over time and may be linked to pathological conditions. The present mini-review describes evidence of AAR and AAI involvement in the misfolding and brain accumulation of Abeta (amyloid beta-peptide), a central event in AD (Alzheimer's disease) synaptic dysfunctions. Structural alterations introduced by site-specific modifications linked to protein aging may affect Abeta production, polymerization and clearance, and therefore play a pivotal role in the pathogenesis of sporadic and genetic forms of AD. Early changes associated with molecular aging also have significant long-term consequences for Abeta folding and turnover. New fast, reproducible and accurate methods for the screening of protein aging markers in biological samples may contribute to improve diagnostic and therapeutic approaches in AD.

  6. Increased levels of 4-hydroxynonenal and acrolein in the brain in preclinical Alzheimer disease.

    Science.gov (United States)

    Bradley, M A; Markesbery, W R; Lovell, M A

    2010-06-15

    Previous studies demonstrate increased levels of 4-hydroxynonenal (HNE) and acrolein in vulnerable brain regions of subjects with mild cognitive impairment and late-stage Alzheimer disease (LAD). Recently preclinical AD (PCAD) subjects, who demonstrate normal antemortem neuropsychological test scores but abundant AD pathology at autopsy, have become the focus of increased study. Levels of extractable HNE and acrolein were quantified by gas chromatography-mass spectrometry with negative chemical ionization, and protein-bound HNE and acrolein were quantified by dot-blot immunohistochemistry in the hippocampus/parahippocampal gyrus (HPG), superior and middle temporal gyri (SMTG), and cerebellum (CER) of 10 PCAD and 10 age-matched normal control (NC) subjects. Results of the analyses show a significant (Pacrolein in the HPG of PCAD subjects compared to age-matched NC subjects and a significant decrease in extractable acrolein in PCAD CER. Significant increases in protein-bound HNE in HPG and a significant decrease in CER of PCAD subjects compared to NC subjects were observed. No significant alterations were observed in either extractable or protein-bound HNE or acrolein in the SMTG of PCAD subjects. Additionally, no significant differences in levels of protein carbonyls were observed in the HPG, SMTG, or CER of PCAD subjects compared to NC subjects. (c) 2010 Elsevier Inc. All rights reserved.

  7. Atherosclerotic lesions and mitochondria DNA deletions in brain microvessels: implication in the pathogenesis of Alzheimer's disease.

    Science.gov (United States)

    Aliev, Gjumrakch; Gasimov, Eldar; Obrenovich, Mark E; Fischbach, Kathryn; Shenk, Justin C; Smith, Mark A; Perry, George

    2008-01-01

    The pathogenesis that is primarily responsible for Alzheimer's disease (AD) and cerebrovascular accidents (CVA) appears to involve chronic hypoperfusion. We studied the ultrastructural features of vascular lesions and mitochondria in brain vascular wall cells from human AD biopsy samples and two transgenic mouse models of AD, yeast artificial chromosome (YAC) and C57B6/SJL Tg (+), which overexpress human amyloid beta precursor protein (AbetaPP). In situ hybridization using probes for normal and 5 kb deleted human and mouse mitochondrial DNA (mtDNA) was performed along with immunocytochemistry using antibodies against the Abeta peptide processed from AbetaPP, 8-hydroxy-2'-guanosine (8OHG), and cytochrome c oxidase (COX). More amyloid deposition, oxidative stress markers as well as mitochondrial DNA deletions and structural abnormalities were present in the vascular walls of the human AD samples and the AbetaPP-YAC and C57B6/SJL Tg (+) transgenic mice compared to age-matched controls. Ultrastructural damage in perivascular cells highly correlated with endothelial lesions in all samples. Therefore, pharmacological interventions, directed at correcting the chronic hypoperfusion state, may change the natural course of the development of dementing neurodegeneration.

  8. Support vector machine-based classification of Alzheimer's disease from whole-brain anatomical MRI

    International Nuclear Information System (INIS)

    Magnin, Benoit; Mesrob, Lilia; Kinkingnehun, Serge; Pelegrini-Issac, Melanie; Colliot, Olivier; Sarazin, Marie; Dubois, Bruno; Lehericy, Stephane; Benali, Habib

    2009-01-01

    We present and evaluate a new automated method based on support vector machine (SVM) classification of whole-brain anatomical magnetic resonance imaging to discriminate between patients with Alzheimer's disease (AD) and elderly control subjects. We studied 16 patients with AD [mean age ± standard deviation (SD)=74.1 ±5.2 years, mini-mental score examination (MMSE) = 23.1 ± 2.9] and 22 elderly controls (72.3±5.0 years, MMSE=28.5± 1.3). Three-dimensional T1-weighted MR images of each subject were automatically parcellated into regions of interest (ROIs). Based upon the characteristics of gray matter extracted from each ROI, we used an SVM algorithm to classify the subjects and statistical procedures based on bootstrap resampling to ensure the robustness of the results. We obtained 94.5% mean correct classification for AD and control subjects (mean specificity, 96.6%; mean sensitivity, 91.5%). Our method has the potential in distinguishing patients with AD from elderly controls and therefore may help in the early diagnosis of AD. (orig.)

  9. Three-dimensional stereotactic surface projection of brain perfusion SPECT improves diagnosis of Alzheimer's disease

    International Nuclear Information System (INIS)

    Honda, Norinari; Machida, Kikuo

    2003-01-01

    Alzheimer's disease (AD) is diagnosed by either inspection of the brain perfusion SPECT, or three-dimensional stereotactic surface display (3D-SSP). The purpose was to compare diagnostic performances of these methods. Sixteen nuclear medicine physicians independently interpreted 99m Tc-ECD SPECT in one session and SPECT with 3D-SSP in another session without clinical information for 50 studies of AD patients and 40 studies of healthy volunteers. Probabilities of AD were reported according to a subjective scale from 0% (normal) to 100% (definite AD). Receiver operating characteristics curves were generated to calculate areas under the receiver operating characteristic (ROC) curves (Az's) for the inspection as well as for an automated diagnosis based on a mean Z value in the bilateral posterior cingulate gyri in a 3D-SSP template. Mean Az for visual interpretation of SPECT alone (0.679±0.058) was significantly smaller than that for visual interpretation of both SPECT and 3D-SSP (0.778±0.060). Az for the automated diagnosis (0.883±0.037) was significantly greater than that for both modes of visual interpretation. 3D-SSP enhanced performance of the nuclear medicine physicians inspecting SPECT. Performance of the automated diagnosis exceeded that of the physicians inspecting SPECT with and without 3D-SSP. (author)

  10. Lacosamide reduces HDAC levels in the brain and improves memory: Potential for treatment of Alzheimer's disease.

    Science.gov (United States)

    Bang, Shraddha R; Ambavade, Shirishkumar D; Jagdale, Priti G; Adkar, Prafulla P; Waghmare, Arun B; Ambavade, Prashant D

    2015-07-01

    Lacosamide, a histone deacetylase (HDAC) inhibitor, has been approved for the treatment of epilepsy. Some HDAC inhibitors have been proven effective for the treatment of memory disorders. The present investigation was designed to evaluate the effect of lacosamide on memory and brain HDAC levels. The effect on memory was evaluated in animals with scopolamine-induced amnesia using the elevated plus maze, object recognition test, and radial arm maze. The levels of acetylcholinesterase and HDAC in the cerebral cortex were evaluated. Lacosamide at doses of 10 and 30mg/kg significantly reduced the transfer latency in the elevated plus maze. Lacosamide at a dose of 30mg/kg significantly increased the time spent with a familiar object in the object recognition test at the 24h interval and decreased the time spent in the baited arm. Moreover, at this dose, the number of errors in the radial arm maze at 3 and 24h intervals was minimized and a reduction in the level of HDAC1, but not acetylcholinesterase, was observed in the cerebral cortex. These effects of lacosamide are equivalent to those of piracetam at a dose of 300mg/kg. These results suggest that lacosamide at a 30mg/kg dose improves disrupted memory, possibly by inhibiting HDAC, and could be used to treat amnesic symptoms of Alzheimer's disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Deep Brain Stimulation for Alzheimer's Disease: Ethical Challenges for Clinical Research.

    Science.gov (United States)

    Siegel, Andrew M; Barrett, Marna S; Bhati, Mahendra T

    2017-01-01

    Deep brain stimulation (DBS) is an invasive neuromodulation modality that has shown early promise as a novel treatment of Alzheimer's disease (AD). Further clinical research is warranted on the basis of positive results from animal and human studies, as well as the inadequacy of existing treatments in reducing the enormous medical and financial costs of untreated AD. Nevertheless, unique ethical challenges require particular attention to elements of subject enrollment and informed consent. Study protocols should specify robust assessment and regular monitoring of subject decision-making capacity to consent to trial participation. Investigators should also assess for and mitigate therapeutic misconception (the phenomenon whereby a research participant conflates the goals of research with those of clinical treatment) and ensure that all prospective trial participants have adequate post-trial access to treatment and DBS device maintenance. In the following discussion, each issue is summarized and followed by recommendations for proper ethical procedure. We conclude by assimilating relevant ethical considerations into a decision-making algorithm designed to aid future clinical investigators of DBS for AD with the task of ethical subject enrollment.

  12. Alzheimer's Disease Facts and Figures

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    Full Text Available ... Dementia >> Home Text size: A A A 2018 Alzheimer's Disease Facts and Figures Download the full report: Download ... worried about memory loss? KNOW THE 10 SIGNS Alzheimer's Disease Facts in Each State The 2018 Alzheimer's Disease ...

  13. Alzheimer's Disease Facts and Figures

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    Full Text Available ... Home Text size: A A A 2018 Alzheimer's Disease Facts and Figures Download the full report: Download ... about memory loss? KNOW THE 10 SIGNS Alzheimer's Disease Facts in Each State The 2018 Alzheimer's Disease ...

  14. Curcumin ameliorates insulin signalling pathway in brain of Alzheimer's disease transgenic mice.

    Science.gov (United States)

    Feng, Hui-Li; Dang, Hui-Zi; Fan, Hui; Chen, Xiao-Pei; Rao, Ying-Xue; Ren, Ying; Yang, Jin-Duo; Shi, Jing; Wang, Peng-Wen; Tian, Jin-Zhou

    2016-12-01

    Deficits in glucose, impaired insulin signalling and brain insulin resistance are common in the pathogenesis of Alzheimer's disease (AD); therefore, some scholars even called AD type 3 diabetes mellitus. Curcumin can reduce the amyloid pathology in AD. Moreover, it is a well-known fact that curcumin has anti-oxidant and anti-inflammatory properties. However, whether or not curcumin could regulate the insulin signal transduction pathway in AD remains unclear. In this study, we used APPswe/PS1dE9 double transgenic mice as the AD model to investigate the mechanisms and the effects of curcumin on AD. Immunohistochemical (IHC) staining and a western blot analysis were used to test the major proteins in the insulin signal transduction pathway. After the administration of curcumin for 6 months, the results showed that the expression of an insulin receptor (InR) and insulin receptor substrate (IRS)-1 decreased in the hippocampal CA1 area of the APPswe/PS1dE9 double transgenic mice, while the expression of phosphatidylinositol-3 kinase (PI3K), phosphorylated PI3K (p-PI3K), serine-threonine kinase (AKT) and phosphorylated AKT (p-AKT) increased. Among the curcumin groups, the medium-dose group was the most effective one. Thus, we believe that curcumin may be a potential therapeutic agent that can regulate the critical molecules in brain insulin signalling pathways. Furthermore, curcumin could be adopted as one of the AD treatments to improve a patient's learning and memory ability. © The Author(s) 2016.

  15. Widespread disruption of functional brain organization in early-onset Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Sofie M Adriaanse

    Full Text Available Early-onset Alzheimer's disease (AD patients present a different clinical profile than late-onset AD patients. This can be partially explained by cortical atrophy, although brain organization might provide more insight. The aim of this study was to examine functional connectivity in early-onset and late-onset AD patients. Resting-state fMRI scans of 20 early-onset (<65 years old, 28 late-onset (≥65 years old AD patients and 15 "young" (<65 years old and 31 "old" (≥65 years old age-matched controls were available. Resting-state network-masks were used to create subject-specific maps. Group differences were examined using a non-parametric permutation test, accounting for gray-matter. Performance on five cognitive domains were used in a correlation analysis with functional connectivity in AD patients. Functional connectivity was not different in any of the RSNs when comparing the two control groups (young vs. old controls, which implies that there is no general effect of aging on functional connectivity. Functional connectivity in early-onset AD was lower in all networks compared to age-matched controls, where late-onset AD showed lower functional connectivity in the default-mode network. Functional connectivity was lower in early-onset compared to late-onset AD in auditory-, sensory-motor, dorsal-visual systems and the default mode network. Across patients, an association of functional connectivity of the default mode network was found with visuoconstruction. Functional connectivity of the right dorsal visual system was associated with attention across patients. In late-onset AD patients alone, higher functional connectivity of the sensory-motor system was associated with poorer memory performance. Functional brain organization was more widely disrupted in early-onset AD when compared to late-onset AD. This could possibly explain different clinical profiles, although more research into the relationship of functional connectivity and cognitive

  16. Cholinergic modulation of visual and attentional brain responses in Alzheimer's disease and in health

    Science.gov (United States)

    Bentley, P.; Driver, J.; Dolan, R.J.

    2008-01-01

    Visuo-attentional deficits occur early in Alzheimer's disease (AD) and are considered more responsive to pro-cholinergic therapy than characteristic memory disturbances. We hypothesised that neural responses in AD during visual attentional processing would be impaired relative to controls, yet partially susceptible to improvement with cholinesterase inhibition. We studied 16 mild AD patients and 17 age-matched healthy controls, using fMRI-scanning to enable within-subject placebo-controlled comparisons of the effects of physostigmine on stimulus- and attention-related brain activations, and to allow between-group comparisons for these. Subjects viewed stimuli comprising faces or buildings while performing a shallow judgement (colour of image) or a deep judgement (young/old age of depicted face or building). Behaviourally, AD subjects performed poorer than controls in both tasks, while physostigmine benefited AD patients for the more demanding age-judgement task. Stimulus-selective (face minus building, and vice versa) BOLD signals in precuneus and posterior parahippocampal cortex were attenuated in AD relative to controls but increased following physostigmine. By contrast, face-selective responses in fusiform cortex were not impaired in AD and showed decreases following physostigmine for both groups. Task-dependent responses in right parietal and prefrontal cortices were diminished in AD but improved following physostigmine. A similar pattern of group and treatment effects was observed in two extrastriate cortical regions that showed enhanced stimulus-selectivity for the deep versus shallow task. Finally, for the healthy group, physostigmine decreased task-dependent effects, partly due to an exaggeration of selectivity during the shallow relative to deep task. Our results demonstrate cholinergic-mediated improvements for both stimulus- and attention-dependent responses in functionally affected extrastriate and frontoparietal regions for AD. We also show that normal

  17. Rey's Auditory Verbal Learning Test scores can be predicted from whole brain MRI in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Elaheh Moradi

    2017-01-01

    Full Text Available Rey's Auditory Verbal Learning Test (RAVLT is a powerful neuropsychological tool for testing episodic memory, which is widely used for the cognitive assessment in dementia and pre-dementia conditions. Several studies have shown that an impairment in RAVLT scores reflect well the underlying pathology caused by Alzheimer's disease (AD, thus making RAVLT an effective early marker to detect AD in persons with memory complaints. We investigated the association between RAVLT scores (RAVLT Immediate and RAVLT Percent Forgetting and the structural brain atrophy caused by AD. The aim was to comprehensively study to what extent the RAVLT scores are predictable based on structural magnetic resonance imaging (MRI data using machine learning approaches as well as to find the most important brain regions for the estimation of RAVLT scores. For this, we built a predictive model to estimate RAVLT scores from gray matter density via elastic net penalized linear regression model. The proposed approach provided highly significant cross-validated correlation between the estimated and observed RAVLT Immediate (R = 0.50 and RAVLT Percent Forgetting (R = 0.43 in a dataset consisting of 806 AD, mild cognitive impairment (MCI or healthy subjects. In addition, the selected machine learning method provided more accurate estimates of RAVLT scores than the relevance vector regression used earlier for the estimation of RAVLT based on MRI data. The top predictors were medial temporal lobe structures and amygdala for the estimation of RAVLT Immediate and angular gyrus, hippocampus and amygdala for the estimation of RAVLT Percent Forgetting. Further, the conversion of MCI subjects to AD in 3-years could be predicted based on either observed or estimated RAVLT scores with an accuracy comparable to MRI-based biomarkers.

  18. Distinct brain networks underlie cognitive dysfunction in Parkinson and Alzheimer diseases

    Science.gov (United States)

    Mattis, Paul J.; Niethammer, Martin; Sako, Wataru; Tang, Chris C.; Nazem, Amir; Gordon, Marc L.; Brandt, Vicky; Dhawan, Vijay

    2016-01-01

    Objective: To determine whether cognitive impairment in Parkinson disease (PD) and Alzheimer disease (AD) derives from the same network pathology. Methods: We analyzed 18F-fluorodeoxyglucose PET scans from 40 patients with AD and 40 age-matched healthy controls from the Alzheimer’s Disease Neuroimaging Initiative and scanned an additional 10 patients with AD and 10 healthy controls at The Feinstein Institute for Medical Research to derive an AD-related metabolic pattern (ADRP) analogous to our previously established PD cognition-related pattern (PDCP) and PD motor-related pattern (PDRP). We computed individual subject expression values for ADRP and PDCP in 89 patients with PD and correlated summary scores for cognitive functioning with network expression. We also evaluated changes in ADRP and PDCP expression in a separate group of 15 patients with PD scanned serially over a 4-year period. Results: Analysis revealed a significant AD-related metabolic topography characterized by covarying metabolic reductions in the hippocampus, parahippocampal gyrus, and parietal and temporal association regions. Expression of ADRP, but not PDCP, was elevated in both AD groups and correlated with worse cognitive summary scores. Patients with PD showed slight ADRP expression, due to topographic overlap with the network underlying PD motor-related pattern degeneration, but only their PDCP expression values increased as cognitive function and executive performance declined. Longitudinal data in PD disclosed an analogous dissociation of network expression. Conclusions: Cognitive dysfunction in PD is associated with a specific brain network that is largely spatially and functionally distinct from that seen in relation to AD. PMID:27708130

  19. Hippocampal Sclerosis of Aging, a Common Alzheimer's Disease 'Mimic': Risk Genotypes are Associated with Brain Atrophy Outside the Temporal Lobe.

    Science.gov (United States)

    Nho, Kwangsik; Saykin, Andrew J; Nelson, Peter T

    2016-01-01

    Hippocampal sclerosis of aging (HS-Aging) is a common brain disease in older adults with a clinical course that is similar to Alzheimer's disease. Four single-nucleotide polymorphisms (SNPs) have previously shown association with HS-Aging. The present study investigated structural brain changes associated with these SNPs using surface-based analysis. Participants from the Alzheimer's Disease Neuroimaging Initiative cohort (ADNI; n = 1,239), with both MRI scans and genotype data, were used to assess the association between brain atrophy and previously identified HS-Aging risk SNPs in the following genes: GRN, TMEM106B, ABCC9, and KCNMB2 (minor allele frequency for each is >30%). A fifth SNP (near the ABCC9 gene) was evaluated in post-hoc analysis. The GRN risk SNP (rs5848_T) was associated with a pattern of atrophy in the dorsomedial frontal lobes bilaterally, remarkable since GRN is a risk factor for frontotemporal dementia. The ABCC9 risk SNP (rs704180_A) was associated with multifocal atrophy whereas a SNP (rs7488080_A) nearby (∼50 kb upstream) ABCC9 was associated with atrophy in the right entorhinal cortex. Neither TMEM106B (rs1990622_T), KCNMB2 (rs9637454_A), nor any of the non-risk alleles were associated with brain atrophy. When all four previously identified HS-Aging risk SNPs were summed into a polygenic risk score, there was a pattern of associated multifocal brain atrophy in a predominately frontal pattern. We conclude that common SNPs previously linked to HS-Aging pathology were associated with a distinct pattern of anterior cortical atrophy. Genetic variation associated with HS-Aging pathology may represent a non-Alzheimer's disease contribution to atrophy outside of the hippocampus in older adults.

  20. Brain Substrates of Learning and Retention in Mild Cognitive Impairment Diagnosis and Progression to Alzheimer's Disease

    Science.gov (United States)

    Chang, Yu-Ling; Bondi, Mark W.; Fennema-Notestine, Christine; McEvoy, Linda K.; Hagler, Donald J., Jr.; Jacobson, Mark W.; Dale, Anders M.

    2010-01-01

    Understanding the underlying qualitative features of memory deficits in mild cognitive impairment (MCI) can provide critical information for early detection of Alzheimer's disease (AD). This study sought to investigate the utility of both learning and retention measures in (a) the diagnosis of MCI, (b) predicting progression to AD, and (c)…

  1. Blood-Brain Barrier Penetrating Biologic TNF-α Inhibitor for Alzheimer's Disease.

    Science.gov (United States)

    Chang, Rudy; Knox, Jillian; Chang, Jae; Derbedrossian, Aram; Vasilevko, Vitaly; Cribbs, David; Boado, Ruben J; Pardridge, William M; Sumbria, Rachita K

    2017-07-03

    Tumor necrosis factor alpha (TNF-α) driven processes are involved at multiple stages of Alzheimer's disease (AD) pathophysiology and disease progression. Biologic TNF-α inhibitors (TNFIs) are the most potent class of TNFIs but cannot be developed for AD since these macromolecules do not cross the blood-brain barrier (BBB). A BBB-penetrating TNFI was engineered by the fusion of the extracellular domain of the type II human TNF receptor (TNFR) to a chimeric monoclonal antibody (mAb) against the mouse transferrin receptor (TfR), designated as the cTfRMAb-TNFR fusion protein. The cTfRMAb domain functions as a molecular Trojan horse, binding to the mouse TfR and ferrying the biologic TNFI across the BBB via receptor-mediated transcytosis. The aim of the study was to examine the effect of this BBB-penetrating biologic TNFI in a mouse model of AD. Six-month-old APPswe, PSEN 1dE9 (APP/PS1) transgenic mice were treated with saline (n = 13), the cTfRMAb-TNFR fusion protein (n = 12), or etanercept (non-BBB-penetrating biologic TNFI; n = 11) 3 days per week intraperitoneally. After 12 weeks of treatment, recognition memory was assessed using the novel object recognition task, mice were sacrificed, and brains were assessed for amyloid beta (Aβ) load, neuroinflammation, BBB damage, and cerebral microhemorrhages. The cTfRMAb-TNFR fusion protein caused a significant reduction in brain Aβ burden (both Aβ peptide and plaque), neuroinflammatory marker ICAM-1, and a BBB disruption marker, parenchymal IgG, and improved recognition memory in the APP/PS1 mice. Fusion protein treatment resulted in low antidrug-antibody formation with no signs of either immune reaction or cerebral microhemorrhage development with chronic 12-week treatment. Chronic treatment with the cTfRMAb-TNFR fusion protein, a BBB-penetrating biologic TNFI, offers therapeutic benefits by targeting Aβ pathology, neuroinflammation, and BBB-disruption, overall improving recognition memory in a transgenic mouse model

  2. How Alzheimer's Changes the Brain

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    Full Text Available ... 54. Osmosis 286,536 views 8:54 ANUGRAH TV 18-03-2018 Sunday HOLY COMMUNION Meeting Live Stream Ankur Narula Ministries 1,685 watching Live now Alzheimer's Prevention Program: Keep Your Brain ...

  3. How Alzheimer's Changes the Brain

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  4. How Alzheimer's Changes the Brain

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    Full Text Available ... Find out why Close How Alzheimer's Changes the Brain National Institute On Aging Loading... Unsubscribe from National ... views 9:29 Loading more suggestions... Show more Language: English Location: United States Restricted Mode: Off History ...

  5. How Alzheimer's Changes the Brain

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  9. Cerebral imaging revealing Alzheimer's disease

    International Nuclear Information System (INIS)

    2011-01-01

    Cerebral imaging is the only non-invasive means of examining the brain and is essential in studying Alzheimer's disease. As a tool for early diagnosis, evaluation and treatment monitoring, this technology is at the heart of the research being done to further improve its reliability and sensitivity. (authors)

  10. Alzheimer disease: An interactome of many diseases

    Directory of Open Access Journals (Sweden)

    Balaji S Rao

    2014-01-01

    Full Text Available Alzheimer Disease (AD is an outcome as well as source of many diseases. Alzheimer is linked with many other diseases like Diabetes type 2, cholesterolemia, hypertension and many more. But how each of these diseases affecting other is still unknown to scientific community. Signaling Pathways of one disease is interlinked with other disease. But to what extent healthy brain is affected when any signaling in human body is disturbed is the question that matters. There is a need of Pathway analysis, Protein-Protein interaction (PPI and the conserved interactome study in AD and linked diseases. It will be helpful in finding the potent drug or vaccine target in conscious manner. In the present research the Protein-Protein interaction of all the proteins involved in Alzheimer Disease is analyzed using ViSANT and osprey tools and pathway analysis further reveals the significant genes/proteins linking AD with other diseases.

  11. [Alzheimer's disease and olfaction].

    Science.gov (United States)

    Naudin, Marine; Mondon, Karl; Atanasova, Boriana

    2013-09-01

    Although olfactory disorders are not at the forefront of the clinical description of Alzheimer's disease (AD), they are common and often overlooked by clinicians and by patients who are largely unaware of their deficits. The past 30 years, the literature has shown early olfactory deficits in AD that is spreading across the olfactory spectrum with disease worsening. Partial overlap between brain areas implies both in olfaction and AD - especially limbic system - motivating these researches. This study describes olfactory parameters and tests using to investigate peripheral (odor threshold) and central (hedonicity, familiarity, intensity, discrimination, identification, olfactory memory) levels. Besides, this article takes an inventory of olfactory disorders in AD including odor threshold, discrimination, identification and olfactory memory capacities with controversial results observed in literature. At last, we discuss which type of olfactory dysfunction could have a clinical interest.

  12. Alzheimer's Disease Facts and Figures

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    Full Text Available ... Alzheimer's >> Home Text size: A A A 2017 Alzheimer's Disease Facts and Figures Download the Full Report: Download ... spending. Take action. Become an advocate SPECIAL REPORT — ALZHEIMER'S DISEASE: THE NEXT FRONTIER In the history of medicine, ...

  13. Brain structure and function related to cognitive reserve variables in normal aging, mild cognitive impairment and Alzheimer's disease.

    Science.gov (United States)

    Solé-Padullés, Cristina; Bartrés-Faz, David; Junqué, Carme; Vendrell, Pere; Rami, Lorena; Clemente, Imma C; Bosch, Beatriu; Villar, Amparo; Bargalló, Núria; Jurado, M Angeles; Barrios, Maite; Molinuevo, Jose Luis

    2009-07-01

    Cognitive reserve (CR) is the brain's capacity to cope with cerebral damage to minimize clinical manifestations. The 'passive model' considers head or brain measures as anatomical substrates of CR, whereas the 'active model' emphasizes the use of brain networks effectively. Sixteen healthy subjects, 12 amnestic mild cognitive impairment (MCI) and 16 cases with mild Alzheimer's disease (AD) were included to investigate the relationships between proxies of CR and cerebral measures considered in the 'passive' and 'active' models. CR proxies were inferred premorbid IQ (WAIS Vocabulary test), 'education-occupation', a questionnaire of intellectual and social activities and a composite CR measure. MRI-derived whole-brain volumes and brain activity by functional MRI during a visual encoding task were obtained. Among healthy elders, higher CR was related to larger brains and reduced activity during cognitive processing, suggesting more effective use of cerebral networks. In contrast, higher CR was associated with reduced brain volumes in MCI and AD and increased brain function in the latter, indicating more advanced neuropathology but that active compensatory mechanisms are still at work in higher CR patients. The right superior temporal gyrus (BA 22) and the left superior parietal lobe (BA 7) showed greatest significant differences in direction of slope with CR and activation between controls and AD cases. Finally, a regression analysis revealed that fMRI patterns were more closely related to CR proxies than brain volumes. Overall, inverse relationships for healthy and pathological aging groups emerged between brain structure and function and CR variables.

  14. Radio electric asymmetric brain stimulation in the treatment of behavioral and psychiatric symptoms in Alzheimer disease

    Directory of Open Access Journals (Sweden)

    Mannu P

    2011-07-01

    Full Text Available Piero Mannu1, Salvatore Rinaldi1,2, Vania Fontani1, Alessandro Castagna11Rinaldi Fontani Institute, Department of Neuro Psycho Physio Pathology, Florence, Italy; 2Medical School of Occupational Medicine, University of Florence, Florence, ItalyPurpose: Behavioral and psychiatric symptoms of dementia (BPSD are common in Alzheimer's disease (AD and disrupt the effective management of AD patients. The present study explores the use of radio electric asymmetric brain stimulation (REAC in patients who have had a poor response to pharmacological treatment.Patients and methods: Eight patients (five females and three males; mean [±standard deviation] age at study baseline: 69.9 ± 3.0 years diagnosed with AD according to the DSM-IV-TR criteria (mean onset age of AD: 65.4 ± 3.5 years were cognitively and psychometrically assessed with the Mini-Mental State Examination (MMSE, the Activity of Daily Living (ADL, the Instrumental Activity of Daily Living (IADL, and the Neuropsychiatric Inventory (NPI, prior to and after each of 2 REAC treatment cycles.Results: Scores on the MMSE and all subscales of the NPI (frequency, severity, and distress, the ADL, and the IADL were significantly improved following the initial REAC treatment. There was further significant improvement in all measurements (with a tendency for improvement in the IADL after the second REAC treatment cycle.Conclusion: The improvement of cognitive and behavioral/psychiatric functioning following REAC treatment suggests that this innovative approach may be an effective, safe, and tolerable alternative to pharmacological treatment of AD patients, especially in the area of BPSD. Elderly patients suffering from other types of dementia may also benefit from REAC treatment.Keywords: anxiety, depression, insomnia, behavioral and psychiatric symptoms of dementia (BPSD

  15. Concordance between brain 18F-FDG PET and cerebrospinal fluid biomarkers in diagnosing Alzheimer's disease.

    Science.gov (United States)

    Rubí, S; Noguera, A; Tarongí, S; Oporto, M; García, A; Vico, H; Espino, A; Picado, M J; Mas, A; Peña, C; Amer, G

    Cortical posterior hypometabolism on PET imaging with 18 F-FDG (FDG-PET), and altered levels of Aß 1-42 peptide, total Tau (tTau) and phosphorylated Tau (pTau) proteins in cerebrospinal fluid (CSF) are established diagnostic biomarkers in Alzheimer's disease (AD). An evaluation has been made of the concordance and relationship between the results of FDG-PET and CSF biomarkers in symptomatic patients with suspected AD. A retrospective review was carried out on 120 patients with cognitive impairment referred to our Cognitive Neurology Unit, and who were evaluated by brain FDG-PET and a lumbar puncture for CSF biomarkers. In order to calculate their Kappa coefficient of concordance, the result of the FDG-PET and the set of the three CSF biomarkers in each patient was classified as normal, inconclusive, or AD-compatible. The relationship between the results of both methods was further assessed using logistic regression analysis, including the Aß 1-42 , tTau and pTau levels as quantitative predictors, and the FDG-PET result as the dependent variable. The weighted Kappa coefficient between FDG-PET and CSF biomarkers was 0.46 (95% CI: 0.35-0.57). Logistic regression analysis showed that the Aß 1-42 and tTau values together were capable of discriminating an FDG-PET result metabolically suggestive of AD from one non-suggestive of AD, with a 91% sensitivity and 93% specificity at the cut-off line Aß 1-42 =44+1.3×tTau. The level of concordance between FDG-PET and CSF biomarkers was moderate, indicating their complementary value in diagnosing AD. The Aß 1-42 and tTau levels in CSF help to predict the patient FDG-PET cortical metabolic status. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  16. Acute aerobic exercise increases brain-derived neurotrophic factor levels in elderly with Alzheimer's disease.

    Science.gov (United States)

    Coelho, Flávia Gomes de Melo; Vital, Thays Martins; Stein, Angelica Miki; Arantes, Franciel José; Rueda, André Veloso; Camarini, Rosana; Teodorov, Elizabeth; Santos-Galduróz, Ruth Ferreira

    2014-01-01

    Studies indicate the involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of Alzheimer's disease (AD). Decreased BDNF levels may constitute a lack of trophic support and contribute to cognitive impairment in AD. The benefits of acute and chronic physical exercise on BDNF levels are well-documented in humans, however, exercise effects on BDNF levels have not been analyzed in older adults with AD. The aim of this study was to investigate the effects of acute aerobic exercise on BDNF levels in older adults with AD and to verify associations among BDNF levels, aerobic fitness, and level of physical activity. Using a controlled design, twenty-one patients with AD (76.3 ± 6.2 years) and eighteen healthy older adults (74.6 ± 4.7 years) completed an acute aerobic exercise. The outcomes included measures of BDNF plasma levels, aerobic fitness (treadmill grade, time to exhaustion, VO2, and maximal lactate) and level of physical activity (Baecke Questionnaire Modified for the Elderly). The independent t-test shows differences between groups with respect to the BDNF plasma levels at baseline (p = 0.04; t = 4.53; df = 37). In two-way ANOVA, a significant effect of time was found (p = 0.001; F = 13.63; df = 37), the aerobic exercise significantly increased BDNF plasma levels in AD patients and healthy controls. A significant correlation (p = 0.04; r = 0.33) was found between BDNF levels and the level of physical activity. The results of our study suggest that aerobic exercise increases BDNF plasma levels in patients with AD and healthy controls. In addition to that, BDNF levels had association with level of physical activity.

  17. How Alzheimer's Changes the Brain

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    Full Text Available ... 556,252 views 13:57 2-Minute Neuroscience: Alzheimer's Disease - Duration: 2:01. Neuroscientifically Challenged 18,542 views ... views 5:15 5 Signs You'll Get Alzheimer's Disease - Dr. Russell Blaylock Offers Crucial Advice. - Duration: 33: ...

  18. How Alzheimer's Changes the Brain

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    Full Text Available ... 599,357 views 13:57 2-Minute Neuroscience: Alzheimer's Disease - Duration: 2:01. Neuroscientifically Challenged 20,532 views 2:01 The 7 Stages of Alzheimer's Disease Through a Caregiver's Eyes - Duration: 54:55. Toni ...

  19. How Alzheimer's Changes the Brain

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    Full Text Available ... to treat and prevent the disease. Category Science & Technology License Standard YouTube License Show more Show less ... Mystery of Alzheimer's Disease - Duration: 4:22. Knoxville News Sentinel 34,722 views 4:22 Alzheimer's and ...

  20. How Alzheimer's Changes the Brain

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    Full Text Available ... 569,749 views 13:57 2-Minute Neuroscience: Alzheimer's Disease - Duration: 2:01. Neuroscientifically Challenged 19,280 views ... 827 views 5:15 The 7 Stages of Alzheimer's Disease Through a Caregiver's Eyes - Duration: 54:55. Toni ...

  1. How Alzheimer's Changes the Brain

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    Full Text Available ... 561,781 views 13:57 2-Minute Neuroscience: Alzheimer's Disease - Duration: 2:01. Neuroscientifically Challenged 18,848 views ... views 5:15 5 Signs You'll Get Alzheimer's Disease - Dr. Russell Blaylock Offers Crucial Advice. - Duration: 33: ...

  2. How Alzheimer's Changes the Brain

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    Full Text Available ... 632,620 views 13:57 2-Minute Neuroscience: Alzheimer's Disease - Duration: 2:01. Neuroscientifically Challenged 21,392 views 2:01 The 7 Stages of Alzheimer's Disease Through a Caregiver's Eyes - Duration: 54:55. Toni ...

  3. How Alzheimer's Changes the Brain

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  4. How Alzheimer's Changes the Brain

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    Full Text Available ... 579,477 views 13:57 2-Minute Neuroscience: Alzheimer's Disease - Duration: 2:01. Neuroscientifically Challenged 19,614 views 2:01 The 7 Stages of Alzheimer's Disease Through a Caregiver's Eyes - Duration: 54:55. Toni ...

  5. Functional brain networks in Alzheimer's disease: EEG analysis based on limited penetrable visibility graph and phase space method

    Science.gov (United States)

    Wang, Jiang; Yang, Chen; Wang, Ruofan; Yu, Haitao; Cao, Yibin; Liu, Jing

    2016-10-01

    In this paper, EEG series are applied to construct functional connections with the correlation between different regions in order to investigate the nonlinear characteristic and the cognitive function of the brain with Alzheimer's disease (AD). First, limited penetrable visibility graph (LPVG) and phase space method map single EEG series into networks, and investigate the underlying chaotic system dynamics of AD brain. Topological properties of the networks are extracted, such as average path length and clustering coefficient. It is found that the network topology of AD in several local brain regions are different from that of the control group with no statistically significant difference existing all over the brain. Furthermore, in order to detect the abnormality of AD brain as a whole, functional connections among different brain regions are reconstructed based on similarity of clustering coefficient sequence (CCSS) of EEG series in the four frequency bands (delta, theta, alpha, and beta), which exhibit obvious small-world properties. Graph analysis demonstrates that for both methodologies, the functional connections between regions of AD brain decrease, particularly in the alpha frequency band. AD causes the graph index complexity of the functional network decreased, the small-world properties weakened, and the vulnerability increased. The obtained results show that the brain functional network constructed by LPVG and phase space method might be more effective to distinguish AD from the normal control than the analysis of single series, which is helpful for revealing the underlying pathological mechanism of the disease.

  6. A multimodal RAGE-specific inhibitor reduces amyloid β-mediated brain disorder in a mouse model of Alzheimer disease.

    Science.gov (United States)

    Deane, Rashid; Singh, Itender; Sagare, Abhay P; Bell, Robert D; Ross, Nathan T; LaRue, Barbra; Love, Rachal; Perry, Sheldon; Paquette, Nicole; Deane, Richard J; Thiyagarajan, Meenakshisundaram; Zarcone, Troy; Fritz, Gunter; Friedman, Alan E; Miller, Benjamin L; Zlokovic, Berislav V

    2012-04-01

    In Alzheimer disease (AD), amyloid β peptide (Aβ) accumulates in plaques in the brain. Receptor for advanced glycation end products (RAGE) mediates Aβ-induced perturbations in cerebral vessels, neurons, and microglia in AD. Here, we identified a high-affinity RAGE-specific inhibitor (FPS-ZM1) that blocked Aβ binding to the V domain of RAGE and inhibited Aβ40- and Aβ42-induced cellular stress in RAGE-expressing cells in vitro and in the mouse brain in vivo. FPS-ZM1 was nontoxic to mice and readily crossed the blood-brain barrier (BBB). In aged APPsw/0 mice overexpressing human Aβ-precursor protein, a transgenic mouse model of AD with established Aβ pathology, FPS-ZM1 inhibited RAGE-mediated influx of circulating Aβ40 and Aβ42 into the brain. In brain, FPS-ZM1 bound exclusively to RAGE, which inhibited β-secretase activity and Aβ production and suppressed microglia activation and the neuroinflammatory response. Blockade of RAGE actions at the BBB and in the brain reduced Aβ40 and Aβ42 levels in brain markedly and normalized cognitive performance and cerebral blood flow responses in aged APPsw/0 mice. Our data suggest that FPS-ZM1 is a potent multimodal RAGE blocker that effectively controls progression of Aβ-mediated brain disorder and that it may have the potential to be a disease-modifying agent for AD.

  7. Multifunctional nanoliposomes with curcumin-lipid derivative and brain targeting functionality with potential applications for Alzheimer disease.

    Science.gov (United States)

    Mourtas, Spyridon; Lazar, Adina N; Markoutsa, Eleni; Duyckaerts, Charles; Antimisiaris, Sophia G

    2014-06-10

    With the objective to formulate multifunctional nanosized liposomes to target amyloid deposits in Alzheimer Disease (AD) brains, a lipid-PEG-curcumin derivative was synthesized and characterized. Multifunctional liposomes incorporating the curcumin derivative and additionally decorated with a Blood Brain Barrier (BBB) transport mediator (anti-Transferin antibody) were prepared and characterized. The fluorescence intensity of curcumin derivative was found to increase notably when the curcumin moiety was in the form of a diisopropylethylamine (DIPEA) salt. Both curcumin-derivative liposomes and curcumin-derivative Anti-TrF liposomes showed a high affinity for the amyloid deposits, on post-mortem brains samples of AD patients. The ability of both liposomes to delay Aβ1-42 peptide aggregation was confirmed by Thioflavin assay. However, the decoration of the curcumin-derivative liposomes with the Anti-TrF improved significantly the intake by the BBB cellular model. Results verify that the attachment of an antibody on the curcumin-liposome surface does not block deposit staining or prevention of Aβ aggregation, while the presence of the curcumin-PEG-lipid conjugate does not reduce their brain-targeting capability substantially, proving the potential of such multifunctional NLs for application in Alzheimer disease treatment and diagnosis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  8. Brain and blood metabolite signatures of pathology and progression in Alzheimer disease: A targeted metabolomics study

    Science.gov (United States)

    Oommen, Anup M.; Varma, Sudhir; Casanova, Ramon; An, Yang; O’Brien, Richard; Pletnikova, Olga; Kastenmueller, Gabi; Doraiswamy, P. Murali; Kaddurah-Daouk, Rima; Thambisetty, Madhav

    2018-01-01

    Background The metabolic basis of Alzheimer disease (AD) is poorly understood, and the relationships between systemic abnormalities in metabolism and AD pathogenesis are unclear. Understanding how global perturbations in metabolism are related to severity of AD neuropathology and the eventual expression of AD symptoms in at-risk individuals is critical to developing effective disease-modifying treatments. In this study, we undertook parallel metabolomics analyses in both the brain and blood to identify systemic correlates of neuropathology and their associations with prodromal and preclinical measures of AD progression. Methods and findings Quantitative and targeted metabolomics (Biocrates AbsoluteIDQ [identification and quantification] p180) assays were performed on brain tissue samples from the autopsy cohort of the Baltimore Longitudinal Study of Aging (BLSA) (N = 44, mean age = 81.33, % female = 36.36) from AD (N = 15), control (CN; N = 14), and “asymptomatic Alzheimer’s disease” (ASYMAD, i.e., individuals with significant AD pathology but no cognitive impairment during life; N = 15) participants. Using machine-learning methods, we identified a panel of 26 metabolites from two main classes—sphingolipids and glycerophospholipids—that discriminated AD and CN samples with accuracy, sensitivity, and specificity of 83.33%, 86.67%, and 80%, respectively. We then assayed these 26 metabolites in serum samples from two well-characterized longitudinal cohorts representing prodromal (Alzheimer’s Disease Neuroimaging Initiative [ADNI], N = 767, mean age = 75.19, % female = 42.63) and preclinical (BLSA) (N = 207, mean age = 78.68, % female = 42.63) AD, in which we tested their associations with magnetic resonance imaging (MRI) measures of AD-related brain atrophy, cerebrospinal fluid (CSF) biomarkers of AD pathology, risk of conversion to incident AD, and trajectories of cognitive performance. We developed an integrated blood and brain endophenotype score that

  9. Mast Cell Activation in Brain Injury, Stress, and Post-traumatic Stress Disorder and Alzheimer's Disease Pathogenesis

    Directory of Open Access Journals (Sweden)

    Duraisamy Kempuraj

    2017-12-01

    Full Text Available Mast cells are localized throughout the body and mediate allergic, immune, and inflammatory reactions. They are heterogeneous, tissue-resident, long-lived, and granulated cells. Mast cells increase their numbers in specific site in the body by proliferation, increased recruitment, increased survival, and increased rate of maturation from its progenitors. Mast cells are implicated in brain injuries, neuropsychiatric disorders, stress, neuroinflammation, and neurodegeneration. Brain mast cells are the first responders before microglia in the brain injuries since mast cells can release prestored mediators. Mast cells also can detect amyloid plaque formation during Alzheimer's disease (AD pathogenesis. Stress conditions activate mast cells to release prestored and newly synthesized inflammatory mediators and induce increased blood-brain barrier permeability, recruitment of immune and inflammatory cells into the brain and neuroinflammation. Stress induces the release of corticotropin-releasing hormone (CRH from paraventricular nucleus of hypothalamus and mast cells. CRH activates glial cells and mast cells through CRH receptors and releases neuroinflammatory mediators. Stress also increases proinflammatory mediator release in the peripheral systems that can induce and augment neuroinflammation. Post-traumatic stress disorder (PTSD is a traumatic-chronic stress related mental dysfunction. Currently there is no specific therapy to treat PTSD since its disease mechanisms are not yet clearly understood. Moreover, recent reports indicate that PTSD could induce and augment neuroinflammation and neurodegeneration in the pathogenesis of neurodegenerative diseases. Mast cells play a crucial role in the peripheral inflammation as well as in neuroinflammation due to brain injuries, stress, depression, and PTSD. Therefore, mast cells activation in brain injury, stress, and PTSD may accelerate the pathogenesis of neuroinflammatory and neurodegenerative diseases

  10. Mast Cell Activation in Brain Injury, Stress, and Post-traumatic Stress Disorder and Alzheimer's Disease Pathogenesis.

    Science.gov (United States)

    Kempuraj, Duraisamy; Selvakumar, Govindhasamy P; Thangavel, Ramasamy; Ahmed, Mohammad E; Zaheer, Smita; Raikwar, Sudhanshu P; Iyer, Shankar S; Bhagavan, Sachin M; Beladakere-Ramaswamy, Swathi; Zaheer, Asgar

    2017-01-01

    Mast cells are localized throughout the body and mediate allergic, immune, and inflammatory reactions. They are heterogeneous, tissue-resident, long-lived, and granulated cells. Mast cells increase their numbers in specific site in the body by proliferation, increased recruitment, increased survival, and increased rate of maturation from its progenitors. Mast cells are implicated in brain injuries, neuropsychiatric disorders, stress, neuroinflammation, and neurodegeneration. Brain mast cells are the first responders before microglia in the brain injuries since mast cells can release prestored mediators. Mast cells also can detect amyloid plaque formation during Alzheimer's disease (AD) pathogenesis. Stress conditions activate mast cells to release prestored and newly synthesized inflammatory mediators and induce increased blood-brain barrier permeability, recruitment of immune and inflammatory cells into the brain and neuroinflammation. Stress induces the release of corticotropin-releasing hormone (CRH) from paraventricular nucleus of hypothalamus and mast cells. CRH activates glial cells and mast cells through CRH receptors and releases neuroinflammatory mediators. Stress also increases proinflammatory mediator release in the peripheral systems that can induce and augment neuroinflammation. Post-traumatic stress disorder (PTSD) is a traumatic-chronic stress related mental dysfunction. Currently there is no specific therapy to treat PTSD since its disease mechanisms are not yet clearly understood. Moreover, recent reports indicate that PTSD could induce and augment neuroinflammation and neurodegeneration in the pathogenesis of neurodegenerative diseases. Mast cells play a crucial role in the peripheral inflammation as well as in neuroinflammation due to brain injuries, stress, depression, and PTSD. Therefore, mast cells activation in brain injury, stress, and PTSD may accelerate the pathogenesis of neuroinflammatory and neurodegenerative diseases including AD. This

  11. Astrocytic Disruption in Traumatic Brain Injury and Alzheimer’s Disease

    Science.gov (United States)

    2014-10-01

    and physiology of hippocampal astrocytes . 15. SUBJECT TERMS Traumatic brain injury, Alzheimer’s disease, astrocytes , reactive astrocytosis, neuronal...neuronal pathologies seen in TBI and AD. Although astrocyte reactivity serves to protect neurons, some normal astrocytic functions including lactate...work. KEYWORDS: Traumatic brain injury, Alzheimer’s disease, astrocytes , reactive astrocytosis, neuronal excitability, monocarboxylate transporters

  12. N-isopropyl I-123 p-iodoamphetamine (IMP) brain SPECT in Alzheimer's disease

    International Nuclear Information System (INIS)

    Momose, Toshimitsu; Nishikawa, Junichi; Kosaka, Noboru; Ohtake, Tohru; Watanabe, Toshiaki; Yoshikawa, Kohki; Iio, Masahiro

    1989-01-01

    Eighteen patients with Alzheimer's disease (AD), 5 patients with Pick disease (PD), 6 patients with other types of degenerative dementia (O) and 12 age-matched normal control subjects (N) were studied using N-isopropyl p-[I-123]iodoamphetamine (I-123 IMP) with SPECT. Regional to cerebellar activity (R/CE) ratio and frontal to parietal (F/R) activity ratio were evaluated in each case. I-123 IMP-SPECT revealed focal abnormality in all cases in AD, PD, O group, while XCT and/or MRI were normal or showed cerebral atrophy without focal abnormal density or intensity. In AD group, R/CE ratio in all the regions except for bilateral Rolandic area and left primary visual cortex were significantly lower (p<0.05 or p<0.01) than that in N group, and F/P ratio were significantly higher (p<0.01) than that in P and O group. In conclusion, I-123 IMP-SPECT is useful to detect focal perfusion abnormality in dementia and may be of value in differentiating Alzheimer's disease from dementia of non-Alzheimer type. (author)

  13. Effects of traumatic brain injury and posttraumatic stress disorder on development of Alzheimer's disease in Vietnam Veterans using the Alzheimer's Disease Neuroimaging Initiative: Preliminary Report.

    Science.gov (United States)

    Weiner, Michael W; Harvey, Danielle; Hayes, Jacqueline; Landau, Susan M; Aisen, Paul S; Petersen, Ronald C; Tosun, Duygu; Veitch, Dallas P; Jack, Clifford R; Decarli, Charles; Saykin, Andrew J; Grafman, Jordan; Neylanthe, Thomas C

    2017-06-01

    Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) have previously been reported to be associated with increased risk of Alzheimer's disease (AD). We are using biomarkers to study Vietnam Veterans with/without mild cognitive impairment with a history of at least one TBI and/or ongoing PTSD to determine whether these contribute to the development of AD. Potential subjects identified by Veterans Administration records underwent an initial telephone screen. Consented subjects underwent clinical evaluation, lumbar puncture, structural MRI and amyloid PET scans. We observed worse cognitive functioning in PTSD and TBI + PTSD groups, worse global cognitive functioning in the PTSD group, lower superior parietal volume in the TBI + PTSD group, and lower amyloid positivity in the PTSD group, but not the TBI group compared to controls without TBI/PTSD. Medial temporal lobe atrophy was not increased in the PTSD and/or TBI groups. Preliminary results do not indicate that TBI or PTSD increase the risk for AD measured by amyloid PET. Additional recruitment, longitudinal follow-up, and tau PET scans will provide more information in the future.

  14. Blood-brain barrier P-glycoprotein function in healthy subjects and Alzheimer's disease patients : Effect of polymorphisms in the ABCB1 gene

    NARCIS (Netherlands)

    D.M.E. van Assema (Daniëlle); M. Lubberink (Mark); P. Rizzu (Patrizia); J.C. van Swieten (John); R.C. Schuit (Robert); J. Eriksson (Joel); P. Scheltens (Philip); M. Koepp (Matthias); A.A. Lammertsma (Adriaan); B.N.M. van Berckel (Bart )

    2012-01-01

    textabstractBackground: P-glycoprotein is a blood-brain barrier efflux transporter involved in the clearance of amyloid-beta from the brain and, as such, might be involved in the pathogenesis of Alzheimer's disease. P-glycoprotein is encoded by the highly polymorphic ABCB1 gene. Single-nucleotide

  15. Blood-brain barrier P-glycoprotein function in healthy subjects and Alzheimer's disease patients: effect of polymorphisms in the ABCB1 gene

    NARCIS (Netherlands)

    van Assema, D.M.E.; Lubberink, J.M.; Rizzu, P.; van Swieten, J.C.; Schuit, R.C.; Eriksson, P.A.J.; Scheltens, P.; Koepp, M.; Lammertsma, A.A.; van Berckel, B.N.M.

    2012-01-01

    Background: P-glycoprotein is a blood-brain barrier efflux transporter involved in the clearance of amyloid-beta from the brain and, as such, might be involved in the pathogenesis of Alzheimer's disease. P-glycoprotein is encoded by the highly polymorphic ABCB1 gene. Single-nucleotide polymorphisms

  16. Alzheimer's Disease Facts and Figures

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    Full Text Available ... health and long-term care costs. worried about memory loss? KNOW THE 10 SIGNS Alzheimer's Disease Facts ... Copyright © 2018 Alzheimer's Association ® . All rights reserved. Our vision is a world without Alzheimer's Formed in 1980, ...

  17. Alzheimer's Disease Facts and Figures

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    Full Text Available ... irrevocable disability occurs. LEARN ABOUT OUR COMMITMENT TO RESEARCH. Read More Alzheimer's Disease Facts in Each State ... news and advances in Alzheimer's treatments, care and research. Get tips for living with Alzheimer's as well ...

  18. Alzheimer's Disease Facts and Figures

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    Full Text Available ... Alzheimer's & Dementia >> Home Text size: A A A 2018 Alzheimer's Disease Facts and Figures Download the full ... all ages are living with Alzheimer's dementia in 2018. This number includes an estimated 5.5 million ...

  19. Alzheimer's Disease Facts and Figures

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    Full Text Available ... Alzheimer's >> Home Text size: A A A 2017 Alzheimer's Disease Facts and Figures Download the Full Report: ... twice as high. Invest in a world without Alzheimer's. Donate Caregivers In 2016, 15.9 million family ...

  20. How Alzheimer's Changes the Brain

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    Full Text Available ... Oil: Ian Blair Hamilton and Cassie Bond - Duration: 9:57. AlkaWay 374,233 views 9:57 Alzheimer's and the Brain - Duration: 15:02. ... blood-brain barrier - Duration: 4:08. Sunnybrook Hospital 9,340 views 4:08 Light-based therapy for ...

  1. Label-free imaging and quantitative chemical analysis of Alzheimer's disease brain samples with multimodal multiphoton nonlinear optical microspectroscopy

    Science.gov (United States)

    Lee, Jang Hyuk; Kim, Dae Hwan; Song, Woo Keun; Oh, Myoung-Kyu; Ko, Do-Kyeong

    2015-05-01

    We developed multimodal multiphoton microspectroscopy using a small-diameter probe with gradient-index lenses and applied it to unstained Alzheimer's disease (AD) brain samples. Our system maintained the image quality and spatial resolution of images obtained using an objective lens of similar numerical aperture. Multicolor images of AD brain samples were obtained simultaneously by integrating two-photon excited fluorescence and second-harmonic generation on a coherent anti-Stokes Raman scattering (CARS) microendoscope platform. Measurements of two hippocampal regions, the cornus ammonis-1 and dentate gyrus, revealed more lipids, amyloid fibers, and collagen in the AD samples than in the normal samples. Normal and AD brains were clearly distinguished by a large spectral difference and quantitative analysis of the CH mode using CARS microendoscope spectroscopy. We expect this system to be an important diagnosis tool in AD research.

  2. How Alzheimer's Changes the Brain

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    Full Text Available ... suggested video will automatically play next. Up next What you can do to prevent Alzheimer's | Lisa Genova - ... 8:54. Osmosis 310,083 views 8:54 What Is Alzheimer's Disease? - Duration: 3:15. AboutAlzOrg 539, ...

  3. How Alzheimer's Changes the Brain

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    Full Text Available ... 728 views 8:54 The 7 Stages of Alzheimer's Disease Through a Caregiver's Eyes - Duration: 54:55. Toni Wombaker 923,094 views 54:55 Kids Meet a Woman with Alzheimer's | Cut - Duration: 5:15. Cut 6,969,600 ...

  4. How Alzheimer's Changes the Brain

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    Full Text Available ... The 7 Stages of Alzheimer's Disease Through a Caregiver's Eyes - Duration: 54:55. Toni Wombaker 923,815 ... 37 Day in the Life of an Alzheimer's Caregiver: Heartbreaking - Duration: 4:39. DavidNazarNews 30,944 views ...

  5. Follow-up of [11C]PIB uptake and brain volume in patients with Alzheimer disease and controls.

    Science.gov (United States)

    Scheinin, N M; Aalto, S; Koikkalainen, J; Lötjönen, J; Karrasch, M; Kemppainen, N; Viitanen, M; Någren, K; Helin, S; Scheinin, M; Rinne, J O

    2009-10-13

    In Alzheimer disease (AD), the accumulation pattern of beta-amyloid over time and its relationship with dementia severity are unclear. We investigated the brain uptake of the amyloid ligand (11)C-labeled Pittsburgh compound B ([(11)C]PIB) and volumetric brain changes over a 2-year follow-up in patients with AD and in aged healthy controls. Fourteen patients with AD (mean age 72 years, SD 6.6) and 13 healthy controls (mean age 68 years, SD 5.4) were examined at baseline and after 2 years (patients with AD: mean 2.0 years, SD 0.2; controls: mean 2.1 years, SD 0.6) with [(11)C]PIB PET, MRI, and neuropsychological assessments. [(11)C]PIB uptake was analyzed with a voxel-based statistical method (SPM), and quantitative data were obtained with automated region-of-interest analysis. MRI data were analyzed with voxel-wise tensor-based morphometry. The [(11)C]PIB uptake of the patients with AD did not increase significantly during follow-up when compared with that of the controls. MRI showed progressive brain volume change in the patients with AD, e.g., in the hippocampal region, temporal cortex, and precuneus (p PIB uptake ratios predicted subsequent volumetric brain changes in the controls (r = 0.725, p = 0.005). The results suggest no (or only little) increase in (11)C-labeled Pittsburgh compound B ([(11)C]PIB) uptake during 2 years of Alzheimer disease progression, despite advancing brain atrophy and declining cognitive performance. Nevertheless, changes in [(11)C]PIB uptake during a longer follow-up cannot be excluded. High cortical [(11)C]PIB uptake may predict ongoing brain atrophy in cognitively normal individuals.

  6. CT study in Alzheimer's disease

    International Nuclear Information System (INIS)

    Arai, Heii; Kobayashi, Kazunari; Ikeda, Kenji; Nagao, Yoshiko; Ogihara, Ryuji; Kosaka, Kenji

    1983-01-01

    Cerebral atrophy on CT was studied in 18 patients with clinically diagnosed Alzheimer's disease and in 14 healthy age-matched subjects as the control. The patients with Alzheimer's disease were divided into three groups of Stages I, Ii and III, according to their clinical symptoms. The study of the measurement method disclosed that the computerized measurement involving calculation of the number of pixels contained within the range of the designated CT numbers is liable to produce errors for the determination of the subarachnoid spaces and the ventricles with calcified colloid plexus. Therefor, for the present study was the method adopted, in which the subarachnoid spaces and the ventricles are measured based on the number of pixels contained in the region of interest by tracing them on the display monitor. Then, both Subarachnoid Space Volume Index (SVI) and Ventricle Volume Index (VVI) were calculated as the indices for cortical atrophy and ventricular dilatation in a slice through the level of the foramen interventriculare Monroi and other three successive ones through upper regions. Cerebral atrophy observed on CT in Alzheimer patients is attributable to Alzheimer's disease processes, rather than to physiological aging of the brain. The degree of the atrophy increases in proportion to the clinical stage, and cortical atrophy is apparent even at Stage I, whereas ventricular dilatation becomes pronounced at later stage. CT is one of effective clinical tests for the diagnosis of Alzheimer's disease. (J.P.N.)

  7. Alzheimer's disease: a practical, psychological approach.

    Science.gov (United States)

    Powell, L S

    1985-01-01

    Alzheimer's Disease affects approximately two million people. It is a crippling, organic brain disorder that causes loss of recent memory, intellectual deterioration, unpredictable behavioral changes, and personality deterioration. The fourth leading cause of death among the elderly, it also affects younger people. The disease has two victims, the Alzheimer patient and the caregiver. Caregivers often experience shame, embarrassment, denial, frustration, anger, depression, and guilt as they care for an Alzheimer patient. This paper provides information about the disease and it's manifestations, along with practical suggestions to help both the Alzheimer patient and the caregiver.

  8. Bilateral deep brain stimulation of the fornix for Alzheimer's disease: surgical safety in the ADvance trial.

    Science.gov (United States)

    Ponce, Francisco A; Asaad, Wael F; Foote, Kelly D; Anderson, William S; Rees Cosgrove, G; Baltuch, Gordon H; Beasley, Kara; Reymers, Donald E; Oh, Esther S; Targum, Steven D; Smith, Gwenn S; Lyketsos, Constantine G; Lozano, Andres M

    2016-07-01

    OBJECT This report describes the stereotactic technique, hospitalization, and 90-day perioperative safety of bilateral deep brain stimulation (DBS) of the fornix in patients who underwent DBS for the treatment of mild, probable Alzheimer's disease (AD). METHODS The ADvance Trial is a multicenter, 12-month, double-blind, randomized, controlled feasibility study being conducted to evaluate the safety, efficacy, and tolerability of DBS of the fornix in patients with mild, probable AD. Intraoperative and perioperative data were collected prospectively. All patients underwent postoperative MRI. Stereotactic analyses were performed in a blinded fashion by a single surgeon. Adverse events (AEs) were reported to an independent clinical events committee and adjudicated to determine the relationship between the AE and the study procedure. RESULTS Between June 6, 2012, and April 28, 2014, a total of 42 patients with mild, probable AD were treated with bilateral fornix DBS (mean age 68.2 ± 7.8 years; range 48.0-79.7 years; 23 men and 19 women). The mean planned target coordinates were x = 5.2 ± 1.0 mm (range 3.0-7.9 mm), y = 9.6 ± 0.9 mm (range 8.0-11.6 mm), z = -7.5 ± 1.2 mm (range -5.4 to -10.0 mm), and the mean postoperative stereotactic radial error on MRI was 1.5 ± 1.0 mm (range 0.2-4.0 mm). The mean length of hospitalization was 1.4 ± 0.8 days. Twenty-six (61.9%) patients experienced 64 AEs related to the study procedure, of which 7 were serious AEs experienced by 5 patients (11.9%). Four (9.5%) patients required return to surgery: 2 patients for explantation due to infection, 1 patient for lead repositioning, and 1 patient for chronic subdural hematoma. No patients experienced neurological deficits as a result of the study, and no deaths were reported. CONCLUSIONS Accurate targeting of DBS to the fornix without direct injury to it is feasible across surgeons and treatment centers. At 90 days after surgery, bilateral fornix DBS was well tolerated by patients with

  9. Currents of memory: recent progress, translational challenges, and ethical considerations in fornix deep brain stimulation trials for Alzheimer's disease.

    Science.gov (United States)

    Viaña, John Noel M; Vickers, James C; Cook, Mark J; Gilbert, Frederic

    2017-08-01

    The serendipitous discovery of triggered autobiographical memories and eventual memory improvement in an obese patient who received fornix deep brain stimulation in 2008 paved the way for several phase I and phase II clinical trials focused on the safety and efficacy of this potential intervention for people with Alzheimer's disease. In this article, we summarize clinical trials and case reports on fornix deep brain stimulation for Alzheimer's disease and review experiments on animal models evaluating the physiological or behavioral effects of this intervention. Based on information from these reports and studies, we identify potential translational challenges of this approach and determine practical and ethical considerations for clinical trials, focusing on issues regarding selection criteria, trial design, and outcome evaluation. Based on initial results suggesting greater benefit for those with milder disease stage, we find it essential that participant expectations are carefully managed to avoid treatment disenchantment and/or frustration from participants and caregivers. Finally, we urge for collaboration between centers to establish proper clinical standards and to promote better trial results comparison. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Analysis of the brain tissues from a patient with Alzheimer's disease and effects of chelating treatment

    International Nuclear Information System (INIS)

    Ektessabi, A.M.; Fujisawa, S.; Takada, K.; Yoshida, K.; Murayama, H.; Shin, R.W.

    1999-01-01

    Alzheimer's, Parkinson's disease and ALS are among major neurodegenerative diseases. The cause of neurodegeneration is unknown, but there are indications that excessive accumulation of essential elements, and sometimes, incorporation of toxic foreign elements in neurons aggravate neurodegeneration. During the past decade, many researchers investigated the causative factors in degenerative diseases to specify genetic or environmental factor. PIXE analysis has been used for these studies because of the sample preparation is easy and detection limit is very low. However, the concentration of matrix elements and foreign elements are extremely low and difficult to detect and to quantify. In this study, specimens from patients with Alzheimer's disease with no chemical treatment, and those with chelating were analyzed. In all analyzed specimens, Na, Al, Si, P, S, Cl, Ca, Ti, Vi, Cr, Fe and Cu were detected. Each specimen in this study consisted of cerebral cortex and substantia alba. From these experiments we can observe a clear tendency that the accumulation of the metal elements use different depending on the constituent tissues, and the method of sample preparation has a dominant role in the measurement results. (author)

  11. 78 FR 66611 - National Alzheimer's Disease Awareness Month, 2013

    Science.gov (United States)

    2013-11-05

    ... National Alzheimer's Disease Awareness Month, 2013 By the President of the United States of America A Proclamation Alzheimer's disease is an irreversible and progressive brain disease that slowly erodes precious..., including senior citizens as well as younger Americans with early-onset Alzheimer's disease. This month, we...

  12. Alzheimer disease brain atrophy subtypes are associated with cognition and rate of decline.

    Science.gov (United States)

    Risacher, Shannon L; Anderson, Wesley H; Charil, Arnaud; Castelluccio, Peter F; Shcherbinin, Sergey; Saykin, Andrew J; Schwarz, Adam J

    2017-11-21

    To test the hypothesis that cortical and hippocampal volumes, measured in vivo from volumetric MRI (vMRI) scans, could be used to identify variant subtypes of Alzheimer disease (AD) and to prospectively predict the rate of clinical decline. Amyloid-positive participants with AD from the Alzheimer's Disease Neuroimaging Initiative (ADNI) 1 and ADNI2 with baseline MRI scans (n = 229) and 2-year clinical follow-up (n = 100) were included. AD subtypes (hippocampal sparing [HpSp MRI ], limbic predominant [LP MRI ], typical AD [tAD MRI ]) were defined according to an algorithm analogous to one recently proposed for tau neuropathology. Relationships between baseline hippocampal volume to cortical volume ratio (HV:CTV) and clinical variables were examined by both continuous regression and categorical models. When participants were divided categorically, the HpSp MRI group showed significantly more AD-like hypometabolism on 18 F-fluorodeoxyglucose-PET ( p Alzheimer's Disease Assessment Scale, 13-Item Subscale (ADAS-Cog 13 ), Mini-Mental State Examination (MMSE), and Functional Assessment Questionnaire (all p < 0.05) and tAD MRI on the MMSE and Clinical Dementia Rating Sum of Boxes (CDR-SB) (both p < 0.05). Finally, a larger HV:CTV was associated with poorer baseline executive function and a faster slope of decline in CDR-SB, MMSE, and ADAS-Cog 13 score ( p < 0.05). These associations were driven mostly by the amount of cortical rather than hippocampal atrophy. AD subtypes with phenotypes consistent with those observed with tau neuropathology can be identified in vivo with vMRI. An increased HV:CTV ratio was predictive of faster clinical decline in participants with AD who were clinically indistinguishable at baseline except for a greater dysexecutive presentation. © 2017 American Academy of Neurology.

  13. How Alzheimer's Changes the Brain

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    Full Text Available ... our bodies against Alzheimer’s | Owen Carmichael | TEDxLSU - Duration: 12:17. TEDx Talks 11,316 views 12:17 Alzheimer's disease - plaques, tangles, causes, symptoms & pathology - ...

  14. Graded perturbations of metabolism in multiple regions of human brain in Alzheimer's disease: Snapshot of a pervasive metabolic disorder.

    Science.gov (United States)

    Xu, Jingshu; Begley, Paul; Church, Stephanie J; Patassini, Stefano; Hollywood, Katherine A; Jüllig, Mia; Curtis, Maurice A; Waldvogel, Henry J; Faull, Richard L M; Unwin, Richard D; Cooper, Garth J S

    2016-06-01

    Alzheimer's disease (AD) is an age-related neurodegenerative disorder that displays pathological characteristics including senile plaques and neurofibrillary tangles. Metabolic defects are also present in AD-brain: for example, signs of deficient cerebral glucose uptake may occur decades before onset of cognitive dysfunction and tissue damage. There have been few systematic studies of the metabolite content of AD human brain, possibly due to scarcity of high-quality brain tissue and/or lack of reliable experimental methodologies. Here we sought to: 1) elucidate the molecular basis of metabolic defects in human AD-brain; and 2) identify endogenous metabolites that might guide new approaches for therapeutic intervention, diagnosis or monitoring of AD. Brains were obtained from nine cases with confirmed clinical/neuropathological AD and nine controls matched for age, sex and post-mortem delay. Metabolite levels were measured in post-mortem tissue from seven regions: three that undergo severe neuronal damage (hippocampus, entorhinal cortex and middle-temporal gyrus); three less severely affected (cingulate gyrus, sensory cortex and motor cortex); and one (cerebellum) that is relatively spared. We report a total of 55 metabolites that were altered in at least one AD-brain region, with different regions showing alterations in between 16 and 33 metabolites. Overall, we detected prominent global alterations in metabolites from several pathways involved in glucose clearance/utilization, the urea cycle, and amino-acid metabolism. The finding that potentially toxigenic molecular perturbations are widespread throughout all brain regions including the cerebellum is consistent with a global brain disease process rather than a localized effect of AD on regional brain metabolism. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  15. Semi-automatic ROI placement system for analysis of brain PET images based on elastic model. Application to diagnosis of Alzheimer's disease

    International Nuclear Information System (INIS)

    Ohyama, Masashi; Mishina, Masahiro; Kitamura, Shin; Katayama, Yasuo; Senda, Michio; Tanizaki, Naoki; Ishii, Kenji

    2000-01-01

    PET with 18F-fluorodeoxyglucose (FDG) is a useful technique to image cerebral glucose metabolism and to detect patients with Alzheimer's disease in the early stage, in which characteristic temporoparietal hypometabolism is visualized. We have developed a new system, in which the standard brain ROI atlas made of networks of segments is elastically transformed to match the subject brain images, so that standard ROIs defined on the segments are placed on the individual brain images and are used to measure radioactivity over each brain region. We applied this methods to Alzheimer's disease. This method was applied to the images of 10 normal subjects (ages 55 +/- 12) and 21 patients clinically diagnosed as Alzheimer's disease (age 61 +/- 10). The FDG uptake reflecting glucose metabolism was evaluated with SUV, i.e. decay corrected radioactivity divided by injected dose per body weight in (Bq/ml)/(Bq/g). The system worked all right in every subject including those with extensive hypometabolism. Alzheimer patients showed markedly lower in the parietal cortex (4.0-4.1). When the threshold value of FDG uptake in the parietal lobe was set as 5 (Bq/ml)/(Bq/g), we could discriminate the patients with Alzheimer's disease from the normal subjects. The sensitivity was 86% and the specificity was 90%. This system can assist diagnosis of FDG images and may be useful for treating data of a large number of subjects; e.g. when PET is applied to health screening. (author)

  16. Brain Regions Involved in Arousal and Reward Processing are Associated with Apathy in Alzheimer's Disease and Frontotemporal Dementia.

    Science.gov (United States)

    Huey, Edward D; Lee, Seonjoo; Cheran, Gayathri; Grafman, Jordan; Devanand, Davangere P

    2017-01-01

    Apathy is a common and problematic symptom of several neurodegenerative illnesses, but its neuroanatomical bases are not understood. To determine the regions associated with apathy in subjects with mild Alzheimer's disease (AD) using a method that accounts for the significant co-linearity of regional atrophy and neuropsychiatric symptoms. We identified 57 subjects with mild AD (CDR = 1) and neuropsychiatric symptoms in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We performed a multivariate multiple regression with LASSO regularization on all symptom subscales of the Neuropsychiatric Inventory and the whole-brain ROI volumes calculated from their baseline MRIs with FreeSurfer. We compared our results to those from a previous study using the same method in patients with frontotemporal dementia (FTD) and corticobasal syndrome (CBS). Of neuropsychiatric symptoms, apathy showed the most robust neuroanatomical associations in the AD subjects. Atrophy of the following regions were independently associated with apathy: the ventromedial prefrontal cortex; ventrolateral prefrontal cortex; posterior cingulate cortex and adjacent lateral cortex; and the bank of the superior temporal sulcus. These results replicate previous studies using FTD and CBS patients, mostly agree with the previous literature on apathy in AD, and correspond to the Medial and Orbital Prefrontal Cortex networks identified in non-human primates. The current study, previous studies from our laboratory, and the previous literature suggest that impairment of the same brain networks involved in arousal, threat response, and reward processing are associated with apathy in AD and FTD.

  17. Trends in brain oxygenation during mental and physical exercise measured using near-infrared spectroscopy (NIRS): potential for early detection of Alzheimer's disease

    Science.gov (United States)

    Allen, Monica S.; Allen, Jeffery W.; Mikkilineni, Shweta; Liu, Hanli

    2005-04-01

    Motivation: Early diagnosis of Alzheimer's disease (AD) is crucial because symptoms respond best to available treatments in the initial stages of the disease. Recent studies have shown that marked changes in brain oxygenation during mental and physical tasks can be used for noninvasive functional brain imaging to detect Alzheimer"s disease. The goal of our study is to explore the possibility of using near infrared spectroscopy (NIRS) and mapping (NIRM) as a diagnostic tool for AD before the onset of significant morphological changes in the brain. Methods: A 16-channel NIRS brain imager was used to noninvasively measure spatial and temporal changes in cerebral hemodynamics induced during verbal fluency task and physical activity. The experiments involved healthy subjects (n = 10) in the age range of 25+/-5 years. The NIRS signals were taken from the subjects' prefrontal cortex during the activities. Results and Conclusion: Trends of oxygenated and deoxygenated hemoglobin in the prefrontal cortex of the brain were observed. During the mental stimulation, the subjects showed significant increase in oxygenated hemoglobin [HbO2] with a simultaneous decrease in deoxygenated hemoglobin [Hb]. However, physical exercise caused a rise in levels of HbO2 with small variations in Hb. This study basically demonstrates that NIRM taken from the prefrontal cortex of the human brain is sensitive to both mental and physical tasks and holds potential to serve as a diagnostic means for early detection of Alzheimer's disease.

  18. Alzheimer's Disease Facts and Figures

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    Full Text Available ... pocket spending. Take action. Become an advocate SPECIAL REPORT — ALZHEIMER'S DISEASE: THE NEXT FRONTIER In the history ... State The 2017 Alzheimer's Disease Facts and Figures report contains data on the impact of this disease ...

  19. Alzheimer's Disease Facts and Figures

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    Full Text Available ... THE 10 SIGNS Alzheimer's Disease Facts in Each State The 2018 Alzheimer's Disease Facts and Figures report ... on the impact of this disease in every state across the nation. Click below to see the ...

  20. Alzheimer's Disease Facts and Figures

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    Full Text Available ... irrevocable disability occurs. LEARN ABOUT OUR COMMITMENT TO RESEARCH. Read More Alzheimer's Disease Facts in Each State The 2017 Alzheimer's Disease Facts and Figures report contains data on the impact of this disease in every ...

  1. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... RESEARCH. Read More Alzheimer's Disease Facts in Each State The 2017 Alzheimer's Disease Facts and Figures report ... on the impact of this disease in every state across the nation. Click below to see the ...

  2. Alzheimer's disease and periodontitis - an elusive link

    Directory of Open Access Journals (Sweden)

    Abhijit N. Gurav

    2014-01-01

    Full Text Available Alzheimer's disease is the preeminent cause and commonest form of dementia. It is clinically characterized by a progressive descent in the cognitive function, which commences with deterioration in memory. The exact etiology and pathophysiologic mechanism of Alzheimer's disease is still not fully understood. However it is hypothesized that, neuroinflammation plays a critical role in the pathogenesis of Alzheimer's disease. Alzheimer's disease is marked by salient inflammatory features, characterized by microglial activation and escalation in the levels of pro-inflammatory cytokines in the affected regions. Studies have suggested a probable role of systemic infection conducing to inflammatory status of the central nervous system. Periodontitis is common oral infection affiliated with gram negative, anaerobic bacteria, capable of orchestrating localized and systemic infections in the subject. Periodontitis is known to elicit a "low grade systemic inflammation" by release of pro-inflammatory cytokines into systemic circulation. This review elucidates the possible role of periodontitis in exacerbating Alzheimer's disease. Periodontitis may bear the potential to affect the onset and progression of Alzheimer's disease. Periodontitis shares the two important features of Alzheimer's disease namely oxidative damage and inflammation, which are exhibited in the brain pathology of Alzheimer's disease. Periodontitis can be treated and hence it is a modifiable risk factor for Alzheimer's disease.

  3. What does the broken brain say to the neuroscientist? Oscillations and connectivity in schizophrenia, Alzheimer's disease, and bipolar disorder.

    Science.gov (United States)

    Başar, E; Schmiedt-Fehr, C; Mathes, B; Femir, B; Emek-Savaş, D D; Tülay, E; Tan, D; Düzgün, A; Güntekin, B; Özerdem, A; Yener, G; Başar-Eroğlu, C

    2016-05-01

    The application of the concept and methods of brain oscillations has been an important research area in neurosciences. In the last decades, besides the application in cognitive processes, the study of changes in brain oscillations in diseases has also become an important focal point of research. In the present paper, some remarkable examples in three different diseases are taken into consideration: 1) schizophrenia (SZ), 2) Alzheimer's disease (AD), 3) bipolar disorders (BD). In the current literature, decreased oscillations in cortical recordings are observed in most of the pathologies. For example, decrease of gamma activity in SZ, decrease of delta activity in almost all diseases, as well as frequency shifts in alpha and the lower frequencies were recorded. However, there are also paradoxical cases in which an increase of oscillatory activities is observed. In BD, whereas alpha activity is greatly decreased, a huge increase of beta activity is observed. Or, in SZ, a paradoxical increase of gamma activity can be observed during cognitive loading. We also observed paradoxical changes in the analysis of connectivity. In AD, we find that alpha, delta, and theta coherences between distant parts of the cortex are greatly decreased, whereas in the gamma band, event-related coherences attain very high values. The comparison of the results and paradoxical changes in diseases may lead to important conclusions related to the web of oscillations and neurotransmitters. In turn, we could gain new insights to approach "brain function", in general. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  4. Improved mitochondrial function in brain aging and Alzheimer disease - the new mechanism of action of the old metabolic enhancer piracetam

    Directory of Open Access Journals (Sweden)

    Kristina Leuner

    2010-09-01

    Full Text Available Piracetam, the prototype of the so-called nootropic drugs’ is used since many years in different countries to treat cognitive impairment in aging and dementia. Findings that piracetam enhances fluidity of brain mitochondrial membranes led to the hypothesis that piracetam might improve mitochondrial function, e.g. might enhance ATP synthesis. This assumption has recently been supported by a number of observations showing enhanced mitochondrial membrane potential (MMP, enhanced ATP production, and reduced sensitivity for apoptosis in a variety of cell and animal models for aging and Alzheimer disease (AD. As a specific consequence, substantial evidence for elevated neuronal plasticity as a specific effect of piracetam has emerged. Taken together, these new findings can explain many of the therapeutic effects of piracetam on cognition in aging and dementia as well as different situations of brain dysfunctions.

  5. Potential neuroimaging biomarkers of pathologic brain changes in Mild Cognitive Impairment and Alzheimer's disease: a systematic review.

    Science.gov (United States)

    Ruan, Qingwei; D'Onofrio, Grazia; Sancarlo, Daniele; Bao, Zhijun; Greco, Antonio; Yu, Zhuowei

    2016-05-16

    Neuroimaging-biomarkers of Mild Cognitive Impairment (MCI) allow an early diagnosis in preclinical stages of Alzheimer's disease (AD). The goal in this paper was to review of biomarkers for Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD), with emphasis on neuroimaging biomarkers. A systematic review was conducted from existing literature that draws on markers and evidence for new measurement techniques of neuroimaging in AD, MCI and non-demented subjects. Selection criteria included: 1) age ≥ 60 years; 2) diagnosis of AD according to NIAAA criteria, 3) diagnosis of MCI according to NIAAA criteria with a confirmed progression to AD assessed by clinical follow-up, and 4) acceptable clinical measures of cognitive impairment, disability, quality of life, and global clinical assessments. Seventy-two articles were included in the review. With the development of new radioligands of neuroimaging, today it is possible to measure different aspects of AD neuropathology, early diagnosis of MCI and AD become probable from preclinical stage of AD to AD dementia and non-AD dementia. The panel of noninvasive neuroimaging-biomarkers reviewed provides a set methods to measure brain structural and functional pathophysiological changes in vivo, which are closely associated with preclinical AD, MCI and non-AD dementia. The dynamic measures of these imaging biomarkers are used to predict the disease progression in the early stages and improve the assessment of therapeutic efficacy in these diseases in future clinical trials.

  6. How Alzheimer's Changes the Brain

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    Full Text Available ... Queue __count__/__total__ It’s YouTube. Uninterrupted. Loading... Want music and videos with zero ads? Get YouTube Red. Working... Not now Try it free Find out why Close How Alzheimer's Changes the Brain National Institute On Aging Loading... Unsubscribe from National ...

  7. Association between fatty acid metabolism in the brain and Alzheimer disease neuropathology and cognitive performance: A nontargeted metabolomic study.

    Directory of Open Access Journals (Sweden)

    Stuart G Snowden

    2017-03-01

    Full Text Available The metabolic basis of Alzheimer disease (AD pathology and expression of AD symptoms is poorly understood. Omega-3 and -6 fatty acids have previously been linked to both protective and pathogenic effects in AD. However, to date little is known about how the abundance of these species is affected by differing levels of disease pathology in the brain.We performed metabolic profiling on brain tissue samples from 43 individuals ranging in age from 57 to 95 y old who were stratified into three groups: AD (N = 14, controls (N = 14 and "asymptomatic Alzheimer's disease" (ASYMAD, i.e., individuals with significant AD neuropathology at death but without evidence for cognitive impairment during life (N = 15 from the autopsy sample of the Baltimore Longitudinal Study of Aging (BLSA. We measured 4,897 metabolite features in regions both vulnerable in the middle frontal and inferior temporal gyri (MFG and ITG and resistant (cerebellum to classical AD pathology. The levels of six unsaturated fatty acids (UFAs in whole brain were compared in controls versus AD, and the differences were as follows: linoleic acid (p = 8.8 x 10-8, FC = 0.52, q = 1.03 x 10-6, linolenic acid (p = 2.5 x 10-4, FC = 0.84, q = 4.03 x 10-4, docosahexaenoic acid (p = 1.7 x 10-7, FC = 1.45, q = 1.24 x 10-6, eicosapentaenoic acid (p = 4.4 x 10-4, FC = 0.16, q = 6.48 x 10-4, oleic acid (p = 3.3 x 10-7, FC = 0.34, q = 1.46 x 10-6, and arachidonic acid (p = 2.98 x 10-5, FC = 0.75, q = 7.95 x 10-5. These fatty acids were strongly associated with AD when comparing the groups in the MFG and ITG, respectively: linoleic acid (p ASYMAD>AD and increases in docosahexanoic acid (AD>ASYMAD>control may represent regionally specific threshold levels of these metabolites beyond which the accumulation of AD pathology triggers the expression of clinical symptoms. The main limitation of this study is the relatively small sample size. There are few cohorts with extensive longitudinal cognitive assessments

  8. Preliminary study of Alzheimer's Disease diagnosis based on brain electrical signals using wireless EEG

    International Nuclear Information System (INIS)

    Handayani, N; Akbar, Y; Khotimah, S N; Haryanto, F; Arif, I; Taruno, W P

    2016-01-01

    This research aims to study brain's electrical signals recorded using EEG as a basis for the diagnosis of patients with Alzheimer's Disease (AD). The subjects consisted of patients with AD, and normal subjects are used as the control. Brain signals are recorded for 3 minutes in a relaxed condition and with eyes closed. The data is processed using power spectral analysis, brain mapping and chaos test to observe the level of complexity of EEG's data. The results show a shift in the power spectral in the low frequency band (delta and theta) in AD patients. The increase of delta and theta occurs in lobus frontal area and lobus parietal respectively. However, there is a decrease of alpha activity in AD patients where in the case of normal subjects with relaxed condition, brain alpha wave dominates the posterior area. This is confirmed by the results of brain mapping. While the results of chaos analysis show that the average value of MMLE is lower in AD patients than in normal subjects. The level of chaos associated with neural complexity in AD patients with lower neural complexity is due to neuronal damage caused by the beta amyloid plaques and tau protein in neurons. (paper)

  9. Mitophagy and Alzheimer's Disease

    DEFF Research Database (Denmark)

    Kerr, Jesse S.; Adriaanse, Bryan A.; Greig, Nigel H.

    2017-01-01

    Neurons affected in Alzheimer's disease (AD) experience mitochondrial dysfunction and a bioenergetic deficit that occurs early and promotes the disease-defining amyloid beta peptide (Aβ) and Tau pathologies. Emerging findings suggest that the autophagy/lysosome pathway that removes damaged...

  10. Alzheimer's Disease Facts and Figures

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    Full Text Available ... irrevocable disability occurs. LEARN ABOUT OUR COMMITMENT TO RESEARCH. Read More Alzheimer's Disease Facts in Each State The 2017 Alzheimer's ... date on the latest news and advances in Alzheimer's treatments, care and research. Get tips for living with Alzheimer's as well ...

  11. Alzheimer's Disease Facts and Figures

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    Full Text Available ... of biomarkers for Alzheimer's disease is making it possible to detect Alzheimer's disease and provide an accurate diagnosis earlier than at any other time in history. In addition to providing significant medical, emotional and ...

  12. Alzheimer's Disease Facts and Figures

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    Full Text Available ... number of important benefits to diagnosed individuals, their caregivers and loved ones, as well as society as a whole. The development of biomarkers for Alzheimer's disease is making it possible to detect Alzheimer's disease ...

  13. Alzheimer's Disease Facts and Figures

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    Full Text Available ... Dementia is one of the costliest conditions to society. Total payments in 2017 for all individuals with ... earliest stages of Alzheimer's disease, we envision a future in which Alzheimer's disease is placed in the ...

  14. Alzheimer's Disease Facts and Figures

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    Full Text Available ... States will develop the disease every 33 seconds. GET INVOLVED. Join the cause Mortality Alzheimer's disease is ... read our security and privacy policy . Plan ahead Get help and support I have Alzheimer's I am ...

  15. Alzheimer's Disease Facts and Figures

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    Full Text Available ... scientific progress is now requiring a change in how we diagnose Alzheimer's disease. Both the National Institute ... priority. It has the potential to markedly change how we diagnose Alzheimer's disease and, as a result, ...

  16. Alzheimer's Disease Facts and Figures

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    Full Text Available ... ALZ | Research | Professionals | We Can Help | Join the Cause alz.org >> Living with Alzheimer's >> Home Text size: ... disease every 33 seconds. GET INVOLVED. Join the cause Mortality Alzheimer's disease is the sixth-leading cause ...

  17. Synchronizing an aging brain: can entraining circadian clocks by food slow Alzheimer's disease?

    Science.gov (United States)

    Kent, Brianne A

    2014-01-01

    Alzheimer's disease (AD) is a global epidemic. Unfortunately, we are still without effective treatments or a cure for this disease, which is having devastating consequences for patients, their families, and societies around the world. Until effective treatments are developed, promoting overall health may hold potential for delaying the onset or preventing neurodegenerative diseases such as AD. In particular, chronobiological concepts may provide a useful framework for identifying the earliest signs of age-related disease as well as inexpensive and noninvasive methods for promoting health. It is well reported that AD is associated with disrupted circadian functioning to a greater extent than normal aging. However, it is unclear if the central circadian clock (i.e., the suprachiasmatic nucleus) is dysfunctioning, or whether the synchrony between the central and peripheral clocks that control behavior and metabolic processes are becoming uncoupled. Desynchrony of rhythms can negatively affect health, increasing morbidity and mortality in both animal models and humans. If the uncoupling of rhythms is contributing to AD progression or exacerbating symptoms, then it may be possible to draw from the food-entrainment literature to identify mechanisms for re-synchronizing rhythms to improve overall health and reduce the severity of symptoms. The following review will briefly summarize the circadian system, its potential role in AD, and propose using a feeding-related neuropeptide, such as ghrelin, to synchronize uncoupled rhythms. Synchronizing rhythms may be an inexpensive way to promote healthy aging and delay the onset of neurodegenerative disease such as AD.

  18. 3D characterization of brain atrophy in Alzheimer's disease and mild cognitive impairment using tensor-based morphometry

    Science.gov (United States)

    Hua, Xue; Leow, Alex D.; Lee, Suh; Klunder, Andrea D.; Toga, Arthur W.; Lepore, Natasha; Chou, Yi-Yu; Brun, Caroline; Chiang, Ming-Chang; Barysheva, Marina; Jack, Clifford R.; Bernstein, Matt A.; Britson, Paula J.; Ward, Chadwick P.; Whitwell, Jennifer L.; Borowski, Bret; Fleisher, Adam S.; Fox, Nick C.; Boyes, Richard G.; Barnes, Josephine; Harvey, Danielle; Kornak, John; Schuff, Norbert; Boreta, Lauren; Alexander, Gene E.; Weiner, Michael W.; Thompson, Paul M.

    2008-01-01

    Tensor-based morphometry (TBM) creates three-dimensional maps of disease-related differences in brain structure, based on nonlinearly registering brain MRI scans to a common image template. Using two different TBM designs (averaging individual differences versus aligning group average templates), we compared the anatomical distribution of brain atrophy in 40 patients with Alzheimer's disease (AD), 40 healthy elderly controls, and 40 individuals with amnestic mild cognitive impairment (aMCI), a condition conferring increased risk for AD. We created an unbiased geometrical average image template for each of the three groups, which were matched for sex and age (mean age: 76.1 years+/−7.7 SD). We warped each individual brain image (N=120) to the control group average template to create Jacobian maps, which show the local expansion or compression factor at each point in the image, reflecting individual volumetric differences. Statistical maps of group differences revealed widespread medial temporal and limbic atrophy in AD, with a lesser, more restricted distribution in MCI. Atrophy and CSF space expansion both correlated strongly with Mini-Mental State Exam (MMSE) scores and Clinical Dementia Rating (CDR). Using cumulative p-value plots, we investigated how detection sensitivity was influenced by the sample size, the choice of search region (whole brain, temporal lobe, hippocampus), the initial linear registration method (9- versus 12-parameter), and the type of TBM design. In the future, TBM may help to (1) identify factors that resist or accelerate the disease process, and (2) measure disease burden in treatment trials. PMID:18378167

  19. Brain Metabolic Dysfunction in Capgras Delusion During Alzheimer's Disease: A Positron Emission Tomography Study.

    Science.gov (United States)

    Jedidi, H; Daury, N; Capa, R; Bahri, M A; Collette, F; Feyers, D; Bastin, C; Maquet, P; Salmon, E

    2015-11-01

    Capgras delusion is characterized by the misidentification of people and by the delusional belief that the misidentified persons have been replaced by impostors, generally perceived as persecutors. Since little is known regarding the neural correlates of Capgras syndrome, the cerebral metabolic pattern of a patient with probable Alzheimer's disease (AD) and Capgras syndrome was compared with those of 24-healthy elderly participants and 26 patients with AD without delusional syndrome. Comparing the healthy group with the AD group, the patient with AD had significant hypometabolism in frontal and posterior midline structures. In the light of current neural models of face perception, our patients with Capgras syndrome may be related to impaired recognition of a familiar face, subserved by the posterior cingulate/precuneus cortex, and impaired reflection about personally relevant knowledge related to a face, subserved by the dorsomedial prefrontal cortex. © The Author(s) 2013.

  20. CNF1 increases brain energy level, counteracts neuroinflammatory markers and rescues cognitive deficits in a murine model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Stefano Loizzo

    Full Text Available Overexpression of pro-inflammatory cytokines and cellular energy failure are associated with neuroinflammatory disorders, such as Alzheimer's disease. Transgenic mice homozygous for human ApoE4 gene, a well known AD and atherosclerosis animal model, show decreased levels of ATP, increased inflammatory cytokines level and accumulation of beta amyloid in the brain. All these findings are considered responsible for triggering cognitive decline. We have demonstrated that a single administration of the bacterial E. coli protein toxin CNF1 to aged apoE4 mice, beside inducing a strong amelioration of both spatial and emotional memory deficits, favored the cell energy restore through an increment of ATP content. This was accompanied by a modulation of cerebral Rho and Rac1 activity. Furthermore, CNF1 decreased the levels of beta amyloid accumulation and interleukin-1β expression in the hippocampus. Altogether, these data suggest that the pharmacological modulation of Rho GTPases by CNF1 can improve memory performances in an animal model of Alzheimer's disease via a control of neuroinflammation and a rescue of systemic energy homeostasis.

  1. Head-to-Head Visual Comparison between Brain Perfusion SPECT and Arterial Spin-Labeling MRI with Different Postlabeling Delays in Alzheimer Disease.

    Science.gov (United States)

    Kaneta, T; Katsuse, O; Hirano, T; Ogawa, M; Yoshida, K; Odawara, T; Hirayasu, Y; Inoue, T

    2017-08-01

    Arterial spin-labeling MR imaging has been recently developed as a noninvasive technique with magnetically labeled arterial blood water as an endogenous contrast medium for the evaluation of CBF. Our aim was to compare arterial spin-labeling MR imaging and SPECT in the visual assessment of CBF in patients with Alzheimer disease. In 33 patients with Alzheimer disease or mild cognitive impairment due to Alzheimer disease, CBF images were obtained by using both arterial spin-labeling-MR imaging with a postlabeling delay of 1.5 seconds and 2.5 seconds (PLD 1.5 and PLD 2.5 , respectively) and brain perfusion SPECT. Twenty-two brain regions were visually assessed, and the diagnostic confidence of Alzheimer disease was recorded. Among all arterial spin-labeling images, 84.9% of PLD 1.5 and 9% of PLD 2.5 images showed the typical pattern of advanced Alzheimer disease (ie, decreased CBF in the bilateral parietal, temporal, and frontal lobes). PLD 1.5 , PLD 2.5 , and SPECT imaging resulted in obviously different visual assessments. PLD 1.5 showed a broad decrease in CBF, which could have been due to an early perfusion. In contrast, PLD 2.5 did not appear to be influenced by an early perfusion but showed fewer pathologic findings than SPECT. The distinctions observed by us should be carefully considered in the visual assessments of Alzheimer disease. Further studies are required to define the patterns of change in arterial spin-labeling-MR imaging associated with Alzheimer disease. © 2017 by American Journal of Neuroradiology.

  2. Alzheimer's Disease Facts and Figures

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    Full Text Available ... Alzheimer's disease is making it possible to detect Alzheimer's disease and provide an accurate diagnosis earlier than at any other time in history. ... to make decisions and share their wishes. Early diagnosis, even ... who will get Alzheimer's disease were diagnosed when they had mild cognitive ...

  3. Novel role of red wine-derived polyphenols in the prevention of Alzheimer's disease dementia and brain pathology: experimental approaches and clinical implications.

    Science.gov (United States)

    Pasinetti, Giulio Maria

    2012-10-01

    Recent studies suggest that by the middle of this century, as many as 14 million Americans will have Alzheimer's disease, creating an enormous strain on families, the health care system and the federal budget. There are still widespread misconceptions about issues related to the prevention and/or treatment of disease pathogenesis, leaving us unprepared to deal with the disease. To address these challenges, several therapeutic approaches are currently under investigation, mainly in an attempt to delay disease onset and eventually slow down its progression. Recent epidemiological evidence has implicated the protective role of dietary polyphenols from grape products against Alzheimer's disease. Furthermore, experimental evidence supports the hypothesis that certain bioactive grape-derived polyphenols may protect against Alzheimer's disease-type cognitive deterioration, in part by interfering with the generation and assembly of β-amyloid peptides into neurotoxic oligomeric aggregated species. Brain-targeting polyphenols have been shown to significantly reduce the generation of β-amyloid peptides in primary cortico-hippocampal neuron cultures, and preliminary results indicate that they may influence neuronal synaptic plasticity. Recent evidence has also implicated the role of certain grape-derived preparations in beneficially modulating tau neuropathology, including reducing tau aggregation. Studies suggest that dietary polyphenolics may benefit Alzheimer's disease by modulating multiple disease-modifying modalities, both β-amyloid-dependent and independent mechanisms, and provide impetus for the development of polyphenolic compounds for Alzheimer's disease prevention and/or therapy. Georg Thieme Verlag KG Stuttgart · New York.

  4. Rivastigmine for Alzheimer's disease.

    Science.gov (United States)

    Birks, Jacqueline S; Chong, Lee Yee; Grimley Evans, John

    2015-09-22

    Alzheimer's disease is the commonest cause of dementia affecting older people. One of the therapeutic strategies aimed at ameliorating the clinical manifestations of Alzheimer's disease is to enhance cholinergic neurotransmission in the brain by the use of cholinesterase inhibitors to delay the breakdown of acetylcholine released into synaptic clefts. Tacrine, the first of the cholinesterase inhibitors to undergo extensive trials for this purpose, was associated with significant adverse effects including hepatotoxicity. Other cholinesterase inhibitors, including rivastigmine, with superior properties in terms of specificity of action and lower risk of adverse effects have since been introduced. Rivastigmine has received approval for use in 60 countries including all member states of the European Union and the USA. To determine the clinical efficacy and safety of rivastigmine for patients with dementia of Alzheimer's type. We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group Specialized Register, on 2 March 2015 using the terms: Rivastigmine OR  exelon OR ENA OR "SDZ ENA 713". ALOIS contains records of clinical trials identified from monthly searches of a number of major healthcare databases (Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS), numerous trial registries and grey literature sources. We included all unconfounded, double-blind, randomised, controlled trials in which treatment with rivastigmine was administered to patients with dementia of the Alzheimer's type for 12 weeks or more and its effects compared with those of placebo in a parallel group of patients, or where two formulations of rivastigmine were compared. One review author (JSB) applied the study selection criteria, assessed the quality of studies and extracted data. A total of 13 trials met the inclusion criteria of the review. The trials had a duration of between 12 and 52 weeks. The older trials tested a capsule form with a dose of up to 12 mg/day. Trials

  5. [How to define Alzheimer's disease].

    Science.gov (United States)

    Poncet, Michel

    2011-09-01

    Alzheimer's disease, which was considered to be a rare disease in subjects aged under 65 until the seventies/eighties, has become a very common disease affecting mostly older subjects. Many consider that it is important to review the meaning of the eponym "Alzheimer's disease", and a revolution, quite literally, is likely to occur. The role of vascular lesions in the onset of dementias among older subjects is widely acknowledged; considering those dementias as Alzheimer's disease may have negative consequences for patient management. Indeed, vascular lesions can be prevented and treated, while Alzheimer's lesions cannot. It may be justified to use "Alzheimer syndrome" instead of "Alzheimer's disease" when vascular risk factors and, all the more so, vascular lesions are present. Significant progress has been made in the understanding of the pathological proteins involved in Alzheimer's disease, as well as their effects on neurons and synapses. However, the etiology of the disease is still unknown, except in the rare hereditary cases, and there is no cure for Alzheimer's disease at present. Clinical research is progressing, and diagnostic criteria for the pre-dementia stage of Alzheimer's disease were suggested. In France, the outstanding Alzheimer plan 2008-2012 should play an important role in enhancing the understanding of Alzheimer's disease, Alzheimer's syndromes and related disorders.

  6. How Alzheimer's Changes the Brain

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    Full Text Available ... to treat and prevent the disease. Category Science & Technology License Standard YouTube License Show more Show less ... Alzheimer's disease - Duration: 4:45. Massachusetts Institute of Technology (MIT) 70,757 views 4:45 Loading more ...

  7. How Alzheimer's Changes the Brain

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    Full Text Available ... at promising ideas to treat and prevent the disease. Category Science & Technology License Standard YouTube License Show ... 104 views 13:57 2-Minute Neuroscience: Alzheimer's Disease - Duration: 2:01. Neuroscientifically Challenged 20,710 views ...

  8. How Alzheimer's Changes the Brain

    Medline Plus

    Full Text Available ... at promising ideas to treat and prevent the disease. Category Science & Technology License Standard YouTube License Show ... 309 views 13:57 2-Minute Neuroscience: Alzheimer's Disease - Duration: 2:01. Neuroscientifically Challenged 20,617 views ...

  9. How Alzheimer's Changes the Brain

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    Full Text Available ... Wombaker 929,392 views 54:55 2-Minute Neuroscience: Alzheimer's Disease - Duration: 2:01. Neuroscientifically Challenged 21, ... disease - Duration: 41:57. The Florey Institute of Neuroscience and Mental Health 2,709 views 41:57 ...

  10. How Alzheimer's Changes the Brain

    Medline Plus

    Full Text Available ... at promising ideas to treat and prevent the disease. Category Science & Technology License Standard YouTube License Show ... 055 views 13:57 2-Minute Neuroscience: Alzheimer's Disease - Duration: 2:01. Neuroscientifically Challenged 20,710 views ...

  11. Hydrogen Sulfide Ameliorates Homocysteine-Induced Alzheimer's Disease-Like Pathology, Blood-Brain Barrier Disruption, and Synaptic Disorder.

    Science.gov (United States)

    Kamat, Pradip K; Kyles, Philip; Kalani, Anuradha; Tyagi, Neetu

    2016-05-01

    Elevated plasma total homocysteine (Hcy) level is associated with an increased risk of Alzheimer's disease (AD). During transsulfuration pathways, Hcy is metabolized into hydrogen sulfide (H2S), which is a synaptic modulator, as well as a neuro-protective agent. However, the role of hydrogen sulfide, as well as N-methyl-D-aspartate receptor (NMDAR) activation, in hyperhomocysteinemia (HHcy) induced blood-brain barrier (BBB) disruption and synaptic dysfunction, leading to AD pathology is not clear. Therefore, we hypothesized that the inhibition of neuronal NMDA-R by H2S and MK801 mitigate the Hcy-induced BBB disruption and synapse dysfunction, in part by decreasing neuronal matrix degradation. Hcy intracerebral (IC) treatment significantly impaired cerebral blood flow (CBF), and cerebral circulation and memory function. Hcy treatment also decreases the expression of cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE) in the brain along with increased expression of NMDA-R (NR1) and synaptosomal Ca(2+) indicating excitotoxicity. Additionally, we found that Hcy treatment increased protein and mRNA expression of intracellular adhesion molecule 1 (ICAM-1), matrix metalloproteinase (MMP)-2, and MMP-9 and also increased MMP-2 and MMP-9 activity in the brain. The increased expression of ICAM-1, glial fibrillary acidic protein (GFAP), and the decreased expression of vascular endothelial (VE)-cadherin and claudin-5 indicates BBB disruption and vascular inflammation. Moreover, we also found decreased expression of microtubule-associated protein 2 (MAP-2), postsynaptic density protein 95 (PSD-95), synapse-associated protein 97 (SAP-97), synaptosomal-associated protein 25 (SNAP-25), synaptophysin, and brain-derived neurotrophic factor (BDNF) showing synapse dysfunction in the hippocampus. Furthermore, NaHS and MK801 treatment ameliorates BBB disruption, CBF, and synapse functions in the mice brain. These results demonstrate a neuro-protective effect of H2S over Hcy

  12. Behavioral syndromes in Alzheimer's disease.

    Science.gov (United States)

    Devanand, D P; Brockington, C D; Moody, B J; Brown, R P; Mayeux, R; Endicott, J; Sackeim, H A

    1992-01-01

    The Behavioral Syndromes Scale for Dementia (BSSD) is a new instrument that showed strong internal consistency and interrater reliability in an outpatient sample of 106 patients with probable Alzheimer's disease. Factor analysis provided support for a priori symptom groupings, particularly the syndromes of disinhibition and apathy-indifference. Dependency (87%), denial of illness (63%), and motor agitation (55%) were common, while sexual disinhibition (2.9%) and self-destructive behaviors (2.9%) were rare. Virtually all symptoms were predominantly minimal to mild in severity. Patients with longer illness duration were more apathetic. Disinhibited behaviors and apathy-indifference increased with greater severity of dementia. Catastrophic reactions, aggression, and agitation were associated with greater functional impairment. There was great heterogeneity in symptom presentation. In Alzheimer's disease, several behavioral changes might be direct manifestations of underlying brain pathology, rather than being solely secondary to cognitive impairment.

  13. Atrophy-specific MRI brain template for Alzheimer's disease and mild cognitive impairment

    DEFF Research Database (Denmark)

    Fonov, Vladimir; Coupe, Pierrick; Eskildsen, Simon Fristed

    and MCI makes use of a single disease-specific template challenging. We propose a novel approach to generate a continuous four-dimensional template, where the 4th dimension is a surrogate measure of overall brain atrophy. Methods We used MRI scans obtained from the ADNI database (www...... of the brain and the contrast between different tissue types for the given level of atrophy. Figure 1 shows images through 6 example values of increasing RLVV. Conclusions The proposed method and resulting template will be useful tools for the development of robust automatic image processing methods targeted.......loni.ucla.edu/ADNI). Automated methods to estimate intracranial capacity (ICC) and lateral ventricles volume (LVV) [2] was applied to all available datasets at base line. The ratio between LVV and ICC (RLVV) was used as a surrogate measure of overall brain atrophy with mean(standard deviation) value of 2.46(0.87)%. Subsets from...

  14. Brain-Derived Neurotrophic Factor Serum Levels and Hippocampal Volume in Mild Cognitive Impairment and Dementia due to Alzheimer Disease

    Directory of Open Access Journals (Sweden)

    Ericksen Mielle Borba

    2016-12-01

    Full Text Available Background/Aims: Hippocampal atrophy is a recognized biomarker of Alzheimer disease (AD pathology. Serum brain-derived neurotrophic factor (BDNF reduction has been associated with neurodegeneration. We aimed to evaluate BDNF serum levels and hippocampal volume in clinical AD (dementia and mild cognitive impairment [MCI]. Methods: Participants were 10 patients with MCI and 13 with dementia due to AD as well as 10 healthy controls. BDNF serum levels were determined by ELISA and volumetric measures with NeuroQuant®. Results: MCI and dementia patients presented lower BDNF serum levels than healthy participants; dementia patients presented a smaller hippocampal volume than MCI patients and healthy participants. Discussion: The findings support that the decrease in BDNF might start before the establishment of neuronal injury expressed by the hippocampal reduction.

  15. Brain-Derived Neurotrophic Factor Serum Levels and Hippocampal Volume in Mild Cognitive Impairment and Dementia due to Alzheimer Disease.

    Science.gov (United States)

    Borba, Ericksen Mielle; Duarte, Juliana Avila; Bristot, Giovana; Scotton, Ellen; Camozzato, Ana Luiza; Chaves, Márcia Lorena Fagundes

    2016-01-01

    Hippocampal atrophy is a recognized biomarker of Alzheimer disease (AD) pathology. Serum brain-derived neurotrophic factor (BDNF) reduction has been associated with neurodegeneration. We aimed to evaluate BDNF serum levels and hippocampal volume in clinical AD (dementia and mild cognitive impairment [MCI]). Participants were 10 patients with MCI and 13 with dementia due to AD as well as 10 healthy controls. BDNF serum levels were determined by ELISA and volumetric measures with NeuroQuant®. MCI and dementia patients presented lower BDNF serum levels than healthy participants; dementia patients presented a smaller hippocampal volume than MCI patients and healthy participants. The findings support that the decrease in BDNF might start before the establishment of neuronal injury expressed by the hippocampal reduction.

  16. Non-invasive brain stimulation to assess and modulate neuroplasticity in Alzheimer's disease.

    Science.gov (United States)

    Boggio, Paulo Sérgio; Valasek, Claudia Aparecida; Campanhã, Camila; Giglio, Ana Carolina Alem; Baptista, Nathalia Ishikawa; Lapenta, Olivia Morgan; Fregni, Felipe

    2011-10-01

    Alzheimer's disease (AD) is a neurodegenerative and progressive disease related to a gradual decline in cognitive functions such as memory, attention, perceptual-spatial abilities, language, and executive functions. Recent evidence has suggested that interventions promoting neural plasticity can induce significant cognitive gains especially in subjects at risk of or with mild AD. Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are non-invasive techniques that can induce significant and long-lasting changes in focal and non-focal neuroplasticity. In this review, we present initial preliminary evidence that TMS and tDCS can enhance performance in cognitive functions typically impaired in AD. Also, we reviewed the initial six studies on AD that presented early findings showing cognitive gains such as in recognition memory and language associated with TMS and tDCS treatment. In addition, we showed that TMS has also been used to assess neuroplasticity changes in AD supporting the notion that cortical excitability is changed in AD due to the neurodegenerative process. Due to the safe profile, cost of these tools, and initial clinical trials results, further studies are warranted in order to replicate and extend the initial findings of rTMS and tDCS as cognitive enhancers in AD. Further trials should explore different targets of stimulation along with different paradigms of stimulation including combination with behavioural interventions.

  17. Putative Role of Red Wine Polyphenols against Brain Pathology in Alzheimer's and Parkinson's Disease.

    Science.gov (United States)

    Caruana, Mario; Cauchi, Ruben; Vassallo, Neville

    2016-01-01

    Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common age-related neurodegenerative disorders and hence pose remarkable socio-economical burdens to both families and state. Although AD and PD have different clinical and neuropathological features, they share common molecular mechanisms that appear to be triggered by multi-factorial events, such as protein aggregation, mitochondrial dysfunction, oxidative stress (OS), and neuroinflammation, ultimately leading to neuronal cell death. Currently, there are no established and validated disease-modifying strategies for either AD or PD. Among the various lifestyle factors that may prevent or slow age-related neurodegenerative diseases, epidemiological studies on moderate consumption of red wine, especially as part of a holistic Mediterranean diet, have attracted increasing interest. Red wine is particularly rich in specific polyphenolic compounds that appear to affect the biological processes of AD and PD, such as quercetin, myricetin, catechins, tannins, anthocyanidins, resveratrol, and ferulic acid. Indeed, there is now a consistent body of in vitro and in vivo data on the neuroprotective effects of red wine polyphenols (RWP) showing that they do not merely possess antioxidant properties, but may additionally act upon, in a multi-target manner, the underlying key mechanisms featuring in both AD and PD. Furthermore, it is important that bioavailability issues are addressed in order for neuroprotection to be relevant in a clinical study scenario. This review summarizes the current knowledge about the major classes of RWP and places into perspective their potential to be considered as nutraceuticals to target neuropathology in AD and PD.

  18. Exercise for the diabetic brain: how physical training may help prevent dementia and Alzheimer's disease in T2DM patients.

    Science.gov (United States)

    Bertram, Sebastian; Brixius, Klara; Brinkmann, Christian

    2016-08-01

    Epidemiological studies indicate that patients with type 2 diabetes mellitus (T2DM) are at increased risk of developing dementia/Alzheimer's disease (AD). This review, which is based on recent studies, presents a molecular framework that links the two diseases and explains how physical training could help counteract neurodegeneration in T2DM patients. Inflammatory, oxidative, and metabolic changes in T2DM patients cause cerebrovascular complications and can lead to blood-brain-barrier (BBB) breakdown. Peripherally increased pro-inflammatory molecules can then pass the BBB more easily and activate stress-activated pathways, thereby promoting key pathological features of dementia/AD such as brain insulin resistance, mitochondrial dysfunction, and accumulation of neurotoxic beta-amyloid (Aβ) oligomers, leading to synaptic loss, neuronal dysfunction, and cell death. Ceramides can also pass the BBB, induce pro-inflammatory reactions, and disturb brain insulin signaling. In a vicious circle, oxidative stress and the pro-inflammatory environment intensify, leading to further cognitive decline. Low testosterone levels might be a common risk factor in T2DM and AD. Regular physical exercise reinforces antioxidative capacity, reduces oxidative stress, and has anti-inflammatory effects. It improves endothelial function and might increase brain capillarization. Physical training can further counteract dyslipidemia and reduce increased ceramide levels. It might also improve Aβ clearance by up-regulating Aβ transporters and, in some cases, increase basal testosterone levels. In addition, regular physical activity can induce neurogenesis. Physical training should therefore be emphasized as a part of prevention programs developed for diabetic patients to minimize the risk of the onset of neurodegenerative diseases among this specific patient group.

  19. Eye Movements in Alzheimer?s Disease

    OpenAIRE

    Molitor, Robert J.; Ko, Philip C.; Ally, Brandon A.

    2015-01-01

    A growing body of literature has investigated changes in eye movements as a result of Alzheimer?s disease (AD). When compared to healthy, age-matched controls, patients display a number of remarkable alterations to oculomotor function and viewing behavior. In this article, we review AD-related changes to fundamental eye movements, such as saccades and smooth pursuit motion, in addition to changes to eye movement patterns during more complex tasks like visual search and scene exploration. We d...

  20. Evidence that a synthetic amyloid-ß oligomer-binding peptide (ABP) targets amyloid-ß deposits in transgenic mouse brain and human Alzheimer's disease brain.

    Science.gov (United States)

    Chakravarthy, Balu; Ito, Shingo; Atkinson, Trevor; Gaudet, Chantal; Ménard, Michel; Brown, Leslie; Whitfield, James

    2014-03-14

    The synthetic ~5 kDa ABP (amyloid-ß binding peptide) consists of a region of the 228 kDa human pericentrioloar material-1 (PCM-1) protein that selectively and avidly binds in vitro Aβ1-42 oligomers, believed to be key co-drivers of Alzheimer's disease (AD), but not monomers (Chakravarthy et al., (2013) [3]). ABP also prevents Aß1-42 from triggering the apoptotic death of cultured human SHSY5Y neuroblasts, likely by sequestering Aß oligomers, suggesting that it might be a potential AD therapeutic. Here we support this possibility by showing that ABP also recognizes and binds Aβ1-42 aggregates in sections of cortices and hippocampi from brains of AD transgenic mice and human AD patients. More importantly, ABP targets Aβ1-42 aggregates when microinjected into the hippocampi of the brains of live AD transgenic mice. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

  1. Alzheimer's Disease Facts and Figures

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    Full Text Available ... advances a biomarker-based method for diagnosis and treatment at the earliest stages of Alzheimer's disease, we ... on the latest news and advances in Alzheimer's treatments, care and research. Get tips for living with ...

  2. Alzheimer's Disease Facts and Figures

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    Full Text Available ... meaning that they care not only for an aging parent, but also for children under age 18. ... diagnose Alzheimer's disease. Both the National Institute on Aging – Alzheimer's Association (NIA-AA) 2011 workgroup and the ...

  3. Alzheimer's Disease Facts and Figures

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    Full Text Available ... Help | Join the Cause alz.org >> Alzheimer's & Dementia >> Home Text size: A A A 2018 Alzheimer's Disease ... people who receive adult day services and nursing home care. Take action. Become an advocate SPECIAL REPORT: ...

  4. Alzheimer's Disease Facts and Figures

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    Full Text Available ... of Alzheimer's. Today, someone in the United States develops Alzheimer's every 65 seconds. By mid-century, someone in the United States will develop the disease every 33 seconds. GET INVOLVED. Join ...

  5. Alzheimer's Disease Facts and Figures

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    Full Text Available ... existing cases of Alzheimer's. Today, someone in the United States develops Alzheimer's every 65 seconds. By mid-century, someone in the United States will develop the disease every 33 seconds. GET ...

  6. Down Syndrome and Alzheimer's Disease

    Science.gov (United States)

    ... A A A Share Plus on Google Plus Alzheimer's & Dementia alz.org | IHaveAlz Overview What Is Dementia ... chapter Join our online community Down Syndrome and Alzheimer's Disease As they age, those affected by Down ...

  7. Alzheimer's Disease Facts and Figures

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    Full Text Available ... Dementia >> Home Text size: A A A 2018 Alzheimer's Disease Facts and Figures Download the full report: ... twice as high. Invest in a world without Alzheimer's. Donate Caregivers Eighty-three percent of the help ...

  8. Alzheimer's Disease Facts and Figures

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    ... Dementia >> Home Text size: A A A 2018 Alzheimer's Disease Facts and Figures Download the full report: ... twice as high. Invest in a world without Alzheimer's. Donate Caregivers Eighty-three percent of the help ...

  9. TREM2 Variants in Alzheimer's Disease

    Science.gov (United States)

    Guerreiro, Rita; Wojtas, Aleksandra; Bras, Jose; Carrasquillo, Minerva; Rogaeva, Ekaterina; Majounie, Elisa; Cruchaga, Carlos; Sassi, Celeste; Kauwe, John S.K.; Younkin, Steven; Hazrati, Lilinaz; Collinge, John; Pocock, Jennifer; Lashley, Tammaryn; Williams, Julie; Lambert, Jean-Charles; Amouyel, Philippe; Goate, Alison; Rademakers, Rosa; Morgan, Kevin; Powell, John; St. George-Hyslop, Peter; Singleton, Andrew; Hardy, John

    2013-01-01

    BACKGROUND Homozygous loss-of-function mutations in TREM2, encoding the triggering receptor expressed on myeloid cells 2 protein, have previously been associated with an autosomal recessive form of early-onset dementia. METHODS We used genome, exome, and Sanger sequencing to analyze the genetic variability in TREM2 in a series of 1092 patients with Alzheimer's disease and 1107 controls (the discovery set). We then performed a meta-analysis on imputed data for the TREM2 variant rs75932628 (predicted to cause a R47H substitution) from three genomewide association studies of Alzheimer's disease and tested for the association of the variant with disease. We genotyped the R47H variant in an additional 1887 cases and 4061 controls. We then assayed the expression of TREM2 across different regions of the human brain and identified genes that are differentially expressed in a mouse model of Alzheimer's disease and in control mice. RESULTS We found significantly more variants in exon 2 of TREM2 in patients with Alzheimer's disease than in controls in the discovery set (P = 0.02). There were 22 variant alleles in 1092 patients with Alzheimer's disease and 5 variant alleles in 1107 controls (P<0.001). The most commonly associated variant, rs75932628 (encoding R47H), showed highly significant association with Alzheimer's disease (P<0.001). Meta-analysis of rs75932628 genotypes imputed from genomewide association studies confirmed this association (P = 0.002), as did direct genotyping of an additional series of 1887 patients with Alzheimer's disease and 4061 controls (P<0.001). Trem2 expression differed between control mice and a mouse model of Alzheimer's disease. CONCLUSIONS Heterozygous rare variants in TREM2 are associated with a significant increase in the risk of Alzheimer's disease. (Funded by Alzheimer's Research UK and others.) PMID:23150934

  10. Biochemical assessment of precuneus and posterior cingulate gyrus in the context of brain aging and Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Chera L Maarouf

    Full Text Available Defining the biochemical alterations that occur in the brain during "normal" aging is an important part of understanding the pathophysiology of neurodegenerative diseases and of distinguishing pathological conditions from aging-associated changes. Three groups were selected based on age and on having no evidence of neurological or significant neurodegenerative disease: 1 young adult individuals, average age 26 years (n = 9; 2 middle-aged subjects, average age 59 years (n = 5; 3 oldest-old individuals, average age 93 years (n = 6. Using ELISA and Western blotting methods, we quantified and compared the levels of several key molecules associated with neurodegenerative disease in the precuneus and posterior cingulate gyrus, two brain regions known to exhibit early imaging alterations during the course of Alzheimer's disease. Our experiments revealed that the bioindicators of emerging brain pathology remained steady or decreased with advancing age. One exception was S100B, which significantly increased with age. Along the process of aging, neurofibrillary tangle deposition increased, even in the absence of amyloid deposition, suggesting the presence of amyloid plaques is not obligatory for their development and that limited tangle density is a part of normal aging. Our study complements a previous assessment of neuropathology in oldest-old subjects, and within the limitations of the small number of individuals involved in the present investigation, it adds valuable information to the molecular and structural heterogeneity observed along the course of aging and dementia. This work underscores the need to examine through direct observation how the processes of amyloid deposition unfold or change prior to the earliest phases of dementia emergence.

  11. How Alzheimer's Changes the Brain

    Medline Plus

    Full Text Available ... to make your opinion count. Sign in 147 2 Don't like this video? Sign in to ... 13:57. TED 615,055 views 13:57 2-Minute Neuroscience: Alzheimer's Disease - Duration: 2:01. Neuroscientifically ...

  12. How Alzheimer's Changes the Brain

    Medline Plus

    Full Text Available ... to make your opinion count. Sign in 128 2 Don't like this video? Sign in to ... 13:57. TED 560,689 views 13:57 2-Minute Neuroscience: Alzheimer's Disease - Duration: 2:01. Neuroscientifically ...

  13. How Alzheimer's Changes the Brain

    Medline Plus

    Full Text Available ... Bredesen, MD - Duration: 1:13:27. Silicon Valley Health Institute 84,533 views 1:13:27 5 ... Disease - Duration: 42:07. All N One Home Health 97,034 views 42:07 Alzheimer's Prevention Program: ...

  14. Curcumin or bisdemethoxycurcumin for nose-to-brain treatment of Alzheimer disease? A bio/chemo-informatics case study.

    Science.gov (United States)

    Hathout, Rania M; El-Ahmady, Sherweit H; Metwally, AbdelKader A

    2017-10-12

    The current study introduces a new idea of utilising several bio/chemoinformatics tools in comparing two bio-similar natural molecules viz. curcumin and bisdemethoxycurcumin (BDMC) in order to select a potential nose-to-brain remedy for Alzheimer disease. The comparison comprised several bio/chemo informatics tools. It encompassed all levels starting from loading the drug in a certain carrier; PLGA nanoparticles, to the biopharmaceutical level investigating the interaction with mucin and inhibition of P-gp blood-brain barrier efflux pumps. Finally, the therapeutic level was investigated by studying the interaction with pharmacological targets such as amyloid peptide plaques and cyclooxygenase2 enzyme responsible for the inflammatory reactions of the studied disease. The comparison revealed the superiority of curcumin over BDMC. Five new analogues were also hypothesised where diethoxybisdemethoxycurcumin was  recommended as a superior molecule. This work introduced the virtual utilisation of bio/chemo informatics tools as a reliable and economic alternative to the exhausting and resources-consuming wet-lab experimentation.

  15. Memory-enhancing and brain protein expression-stimulating effects of novel calcium antagonist in Alzheimer's disease transgenic female mice.

    Science.gov (United States)

    Jansone, Baiba; Kadish, Inga; van Groen, Thomas; Beitnere, Ulrika; Plotniece, Aiva; Pajuste, Karlis; Klusa, Vija

    2016-11-01

    The prevalence of Alzheimer's disease (AD) is higher in females than in males, and causes more severe cognitive, memory and behavioral impairments. Previously, in male transgenic (Tg) APPSweDI mice, we reported that the novel lipophilic 1,4-dihydropyridine (DHP) derivative AP-12 crossed the blood-brain barrier, blocked neuronal and vascular calcium channels, changed brain protein expression and improved behavior. In this study, we used female Tg APPSweDI mice to assess the effects of AP-12 on behavior, and brain protein expression, with a particular focus on those of the GABAergic system. The results showed that in female Tg mice, similar to male Tg mice, AP-12 improved spatial learning/memory performance in the water maze test and demonstrated anxiolytic effect in the elevated zero maze (after single administration of AP-12) and elevated plus maze (after chronic injections of AP-12). In addition, we demonstrated upregulated expression of glutamate decarboxylase 67 (GAD67) and vesicular GABA transporter (VGAT) in the cingulate cortex and hippocampus, pointing to the role of the GABAergic system as one of the neural networks dysregulated in AD. In both female and male mice, AP-12 did not change the expression of hippocampal Homer-1, a protein which is involved in synaptic plasticity. However, in cingulate cortex, the staining density of Homer-1 was significantly increased in female mice. Further, female mice (similar to male mice) did not show changes in brain AChE expression and in the amyloid beta load in the hippocampus and cingulate cortex. In conclusion, the memory enhancing, anxiolytic and protein expression effects of AP-12 did not show sex specificity in APPSweDI mice. Considering the ability of AP-12 to block brain calcium channels and improve memory by enhancing the GABAergic and synaptic plasticity processes, AP-12 is a promising compound which merits further pre-clinical studies to investigate its usefulness in the treatment of AD. Copyright © 2016

  16. A novel LDL-mimic nanocarrier for the targeted delivery of curcumin into the brain to treat Alzheimer's disease.

    Science.gov (United States)

    Meng, Fanfei; Asghar, Sajid; Gao, Shiya; Su, Zhigui; Song, Jue; Huo, Meirong; Meng, Weidong; Ping, Qineng; Xiao, Yanyu

    2015-10-01

    In this study, a novel low density lipoprotein (LDL)-mimic nanostructured lipid carrier (NLC) modified with lactoferrin (Lf) and loaded with curcumin (Cur) was designed for brain-targeted delivery, and its effect on controlling the progression of Alzheimer's disease (AD) in rats was evaluated. NLC with the composition resembling the lipid portion of LDL was prepared by using solvent evaporation method. Lf was adsorbed onto the surface of NLC via electrostatic interaction to yield Lf modified-NLC (Lf-mNLC) as the LDL-mimic nanocarrier. In order to make sure more Lf was adsorbed on the surface of NLC, negatively charged carboxylated polyethylene glycol (100) monostearate (S100-COOH) was synthesized and anchored into NLC. Different levels of S100-COOH (0-0.02 mmol) and Lf modified NLC (0.5-2.5 mg/mL of Lf solution) were prepared and characterized. The uptake and potential cytotoxicities of different preparations were investigated in the brain capillary endothelial cells (BCECs). An AD model of rats was employed to evaluate the therapeutic effects of Lf-mNLC. The results indicate that Lf-mNLC with a high level of Lf showed the maximum uptake in BCECs (1.39 folds greater than NLC) as cellular uptake of Lf-mNLC by BCECs was found to be mediated by the Lf receptor. FRET studies showed Cur still wrapped inside NLC after uptake by BCECs, demonstrating stability of the carrier as it moved across the BBB. Ex vivo imaging studies exposed Lf-mNLC could effectively permeate BBB and preferentially accumulate in the brain (2.78 times greater than NLC). Histopathological evaluation confirmed superior efficacy of Lf-mNLC in controlling the damage associated with AD. In conclusion, Lf-mNLC is a promising drug delivery system for targeting therapy of brain disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Metabolic interaction between ApoE genotype and onset age in Alzheimer's disease: implications for brain reserve

    Science.gov (United States)

    Mosconi, L; Herholz, K; Prohovnik, I; Nacmias, B; De Cristofaro, M T R; Fayyaz, M; Bracco, L; Sorbi, S; Pupi, A

    2005-01-01

    Background: Clinically apparent Alzheimer's disease (AD) is thought to result when brain tissue damage exceeds a critical threshold of "brain reserve", a process possibly accelerated by the apolipoprotein E (ApoE) E4 allele. The interaction between onset age and ApoE genotype was investigated to assess whether early disease onset (<65 years) in patients carrying the E4 allele is associated with greater cerebral metabolic (regional cerebral metabolic rate of glucose utilisation, rCMRgl) reduction. Methods: AD patients, divided into early (EOAD; 27 patients) and late onset (LOAD; 65 patients) groups, both groups balanced as to the number of E4 carriers (E4+) and non-carriers (E4–), and matched controls (NC; 35 cases) underwent 18F-FDG PET ([18F]fluorodeoxyglucose positron emission tomography) scanning. SPM'99 software was used to compare AD patients to NC and to perform a two way ANOVA with onset age and ApoE genotype as grouping factors. Results were considered significant at p<0.001, uncorrected. Results: AD patients demonstrated rCMRgl reductions compared to NC, with rCMRgl lower in association cortex and relatively higher in limbic areas in EOAD compared to LOAD subjects. rCMRgl was lower in the anterior cingulate and frontal cortex for E4+ compared to E4– subjects. A significant onset age by ApoE interaction was detected in the hippocampi and basal frontal cortex, with EOAD E4+ subjects having the greatest rCMRgl reduction. Conclusions: The interactive effects of early onset age, possibly reflecting lower brain reserve, and ApoE E4 allele, possibly leading to greater tissue damage, lead to reduced tolerance to the pathophysiological effects of AD in key brain regions. PMID:15607989

  18. Microspectroscopy (μFTIR) reveals co-localization of lipid oxidation and amyloid plaques in human Alzheimer disease brains.

    Science.gov (United States)

    Benseny-Cases, Núria; Klementieva, Oxana; Cotte, Marine; Ferrer, Isidre; Cladera, Josep

    2014-12-16

    Amyloid peptides are the main component of one of the characteristic pathological hallmarks of Alzheimer's disease (AD): senile plaques. According to the amyloid cascade hypothesis, amyloid peptides may play a central role in the sequence of events that leads to neurodegeneration. However, there are other factors, such as oxidative stress, that may be crucial for the development of the disease. In the present paper, we show that it is possible, by using Fourier tranform infrared (FTIR) microscopy, to co-localize amyloid deposits and lipid peroxidation in tissue slides from patients affected by Alzheimer's disease. Plaques and lipids can be analyzed in the same sample, making use of the characteristic infrared bands for peptide aggregation and lipid oxidation. The results show that, in samples from patients diagnosed with AD, the plaques and their immediate surroundings are always characterized by the presence of oxidized lipids. As for samples from non-AD individuals, those without amyloid plaques show a lower level of lipid oxidation than AD individuals. However, it is known that plaques can be detected in the brains of some non-AD individuals. Our results show that, in such cases, the lipid in the plaques and their surroundings display oxidation levels that are similar to those of tissues with no plaques. These results point to lipid oxidation as a possible key factor in the path that goes from showing the typical neurophatological hallmarks to suffering from dementia. In this process, the oxidative power of the amyloid peptide, possibly in the form of nonfibrillar aggregates, could play a central role.

  19. FDG-PET changes in brain glucose metabolism from normal cognition to pathologically verified Alzheimer's disease

    International Nuclear Information System (INIS)

    Mosconi, Lisa; Mistur, Rachel; Switalski, Remigiusz; Glodzik, Lidia; Li, Yi; Pirraglia, Elizabeth; De Santi, Susan; Reisberg, Barry; Tsui, Wai Hon; De Leon, Mony J.; Wisniewski, Thomas

    2009-01-01

    We report the first clinicopathological series of longitudinal FDG-PET scans in post-mortem (PM) verified cognitively normal elderly (NL) followed to the onset of Alzheimer's-type dementia (DAT), and in patients with mild DAT with progressive cognitive deterioration. Four NL subjects and three patients with mild DAT received longitudinal clinical, neuropsychological and dynamic FDG-PET examinations with arterial input functions. NL subjects were followed for 13 ± 5 years, received FDG-PET examinations over 7 ± 2 years, and autopsy 6 ± 3 years after the last FDG-PET. Two NL declined to mild cognitive impairment (MCI), and two developed probable DAT before death. DAT patients were followed for 9 ± 3 years, received FDG-PET examinations over 3 ± 2 years, and autopsy 7 ± 1 years after the last FDG-PET. Two DAT patients progressed to moderate-to-severe dementia and one developed vascular dementia. The two NL subjects who declined to DAT received a PM diagnosis of definite AD. Their FDG-PET scans indicated a progression of deficits in the cerebral metabolic rate for glucose (CMRglc) from the hippocampus to the parietotemporal and posterior cingulate cortices. One DAT patient showed AD with diffuse Lewy body disease (LBD) at PM, and her last in vivo PET was indicative of possible LBD for the presence of occipital as well as parietotemporal hypometabolism. Progressive CMRglc reductions on FDG-PET occur years in advance of clinical DAT symptoms in patients with pathologically verified disease. The FDG-PET profiles in life were consistent with the PM diagnosis. (orig.)

  20. Reduced N-acetylaspartate content in the frontal part of the brain in patients with probable Alzheimer's disease

    DEFF Research Database (Denmark)

    Christiansen, P; Schlosser, A; Henriksen, O

    1995-01-01

    with probable Alzheimer's disease. Eight age-matched healthy volunteers served as controls. Furthermore, T1 and T2 relaxation times of the metabolites and signal ratios: NAA/Cho, NAA/[Cr + PCr], and [Cr + PCr]/Cho at four different echo times (TE) and two different repetition times (TR) were calculated....... The experiments were carried out using a Siemens Helicon SP 63/84 wholebody MR-scanner at 1.5 T. The concentration of NAA was significantly lower in the patients with probable Alzheimer's disease than in the healthy volunteers. No significant difference was found for any other metabolite concentration....... For the signal ratios the only statistically significant difference was that the NAA/Cho ratio at TE = 92 ms and TR = 1.6 s was lower in the patients with probable Alzheimer's disease compared with the control group. A trend towards a longer T2 relaxation time for NAA in the patients with probable Alzheimer...

  1. [Palliative care and Alzheimer disease].

    Science.gov (United States)

    Lopez-Tourres, F; Lefebvre-Chapiro, S; Fétéanu, D; Trivalle, C

    2009-06-01

    Although end-of-life care is a relatively common option for patients with terminal cancer, it has become available only recently for patients with Alzheimer's disease. Alzheimer's disease is a chronic process of gradual deterioration of cognitive ability and the resulting deficits in activities of daily living. The chronic disease course of Alzheimer's disease gives to the clinician the opportunity to look ahead and plan for the final stages of care. This article presents a review of palliative care interventions for patients with Alzheimer's disease and other dementias. End-of-life care for individuals with end-stage Alzheimer's disease is increasingly important because of the increasing number of patients with this disease. However, there are barriers to providing high-quality end-of-life care. Currently, palliative care is not optimal for Alzheimer's patients. Health care systems and clinicians should make efforts to improve the suffering of patients with this disease and their caregivers.

  2. Semi-automatic ROI placement system for analysis of brain PET images based on elastic model. Application to diagnosis of Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Ohyama, Masashi; Mishina, Masahiro; Kitamura, Shin; Katayama, Yasuo [Nippon Medical School, Tokyo (Japan); Senda, Michio; Tanizaki, Naoki; Ishii, Kenji

    2000-02-01

    PET with 18F-fluorodeoxyglucose (FDG) is a useful technique to image cerebral glucose metabolism and to detect patients with Alzheimer's disease in the early stage, in which characteristic temporoparietal hypometabolism is visualized. We have developed a new system, in which the standard brain ROI atlas made of networks of segments is elastically transformed to match the subject brain images, so that standard ROIs defined on the segments are placed on the individual brain images and are used to measure radioactivity over each brain region. We applied this methods to Alzheimer's disease. This method was applied to the images of 10 normal subjects (ages 55 +/- 12) and 21 patients clinically diagnosed as Alzheimer's disease (age 61 +/- 10). The FDG uptake reflecting glucose metabolism was evaluated with SUV, i.e. decay corrected radioactivity divided by injected dose per body weight in (Bq/ml)/(Bq/g). The system worked all right in every subject including those with extensive hypometabolism. Alzheimer patients showed markedly lower in the parietal cortex (4.0-4.1). When the threshold value of FDG uptake in the parietal lobe was set as 5 (Bq/ml)/(Bq/g), we could discriminate the patients with Alzheimer's disease from the normal subjects. The sensitivity was 86% and the specificity was 90%. This system can assist diagnosis of FDG images and may be useful for treating data of a large number of subjects; e.g. when PET is applied to health screening. (author)

  3. Tacrine for Alzheimer's disease.

    Science.gov (United States)

    Qizilbash, N; Birks, J; López-Arrieta, J; Lewington, S; Szeto, S

    2000-01-01

    Tacrine is one of the first drugs to be widely marketed for the loss of memory and intellectual decline in Alzheimer's disease. The alleged success of tacrine in the treatment of these symptoms has been heralded as confirmation of the cholinergic theory of Alzheimer's disease. However, the efficacy of tacrine for symptoms of dementia remains controversial. This is reflected by the low rate of prescription of tacrine in countries where it is approved and the lack of approval by several regulatory authorities in Europe and elsewhere. The uncertainty about the efficacy of tacrine is due to the difficulties in interpretation of the results from the clinical trials. The reasons for this are the small effects of tacrine compared to placebo for all outcomes; the high incidence of adverse events; the lack of benefit observed in several trials; the use of cross-over designs and their associated methodological problems in a disease like dementia; the use of different measurement scales to assess outcome in different trials; and the problem of high dropout rates. To determine the clinical efficacy of tacrine for the symptoms of Alzheimer's disease. The Cochrane Dementia Group Register of Clinical Trials was searched using the terms 'tacrine', 'tetrahydroaminoacridine' and 'THA' (see the Group's search strategy for full details). All unconfounded, double-blind, randomized trials in which treatment with tacrine was administered for more than a day and compared to placebo in patients with dementia of the Alzheimer's type. Data were extracted independently by two reviewers, pooled if appropriate and possible, and the pooled odds ratios (95%CI) or the average differences (95%CI) were estimated. Where possible, intention-to-treat data were used. This review produced no clear results. The results were compatible with tacrine producing improvement, no change or even harm for those with Alzheimer's disease. It was not possible to use many of the published results in a combined

  4. Oligodendrocytes and Alzheimer's disease.

    Science.gov (United States)

    Cai, Zhiyou; Xiao, Ming

    2016-01-01

    Extensive evidence has indicated that the breakdown of myelin is associated with Alzheimer's disease (AD) since the vulnerability of oligodendrocytes under Alzheimer's pathology easily induces the myelin breakdown and the loss of the myelin sheath which might be the initiating step in the changes of the earliest stage of AD prior to appearance of amyloid and tau pathology. Considerable research implicated that beta-amyloid (Aβ)-mediated oligodendrocyte dysfunction and myelin breakdown may be via neuroinflammation, oxidative stress and/or apoptosis. It also seems that the oligodendrocyte dysfunction is triggered by the formation of neurofibrillary tangles (NFTs) through inflammation and oxidative stress as the common pathophysiological base. Impaired repair of oligodendrocyte precursor cells (OPCs) might possibly enhance the disease progress under decreased self-healing ability from aging process and pathological factors including Aβ pathology and/or NFTs. Thus, these results have suggested that targeting oligodendrocytes may be a novel therapeutic intervention for the prevention and treatment of AD.

  5. [Calcium hypothesis of Alzheimer disease].

    Science.gov (United States)

    Riazantseva, M A; Mozhaeva, G N; Kaznacheeva, E V

    2012-01-01

    Alzheimer's disease is the most common neurodegenerative disorder characterized by progressive memory and cognitive abilities loss. The etiology of Alzheimer's disease is poorly understood. In this regard, there is no effective treatment for the disease. Various hypotheses to explain the nature of the pathology of Alzheimer's disease led to the development of appropriate therapeutics. Despite of decades of research and clinical trials available therapeutics, at best, can only slow down the progression of the disease, but cannot cure it. This review dedicated to the one of modern hypotheses of Alzheimer's disease pathogenesis implied the impairment of calcium homeostasis as a key event for the development of neurodegenerative processes.

  6. Apathy in Alzheimer's disease

    OpenAIRE

    Nobis, L; Husain, M

    2017-01-01

    Apathy is the most common neuropsychiatric symptom in patients with Alzheimer's disease (AD). The presence of apathy has been related to greater caregiver distress, decreased quality of life, and increased morbidity. Here we review the most recent studies on this neuropsychiatric syndrome, focusing on prevalence, impact on quality of life, behavioural and neuroimaging studies, and treatment options. The results of some investigations on the behavioural and neuroanatomical profile of apathy in...

  7. Cognitive reserve in ageing and Alzheimer's disease

    OpenAIRE

    Stern, Yaakov

    2012-01-01

    The concept of reserve accounts for individual differences in susceptibility to age-related brain changes or Alzheimer's disease-related pathology. There is evidence that some people can tolerate more of these changes than others and still maintain function. Epidemiologic studies suggest that lifetime exposures including educational and occupational attainment, and leisure activities in late life, can increase this reserve. For example, there is a reduced risk of developing Alzheimer's diseas...

  8. A comparison of early diagnostic utility of Alzheimer disease biomarkers in brain magnetic resonance and cerebrospinal fluid.

    Science.gov (United States)

    Monge Argilés, J A; Blanco Cantó, M A; Leiva Salinas, C; Flors, L; Muñoz Ruiz, C; Sánchez Payá, J; Gasparini Berenguer, R; Leiva Santana, C

    2014-09-01

    The goals of this study were to compare the early diagnostic utility of Alzheimer disease biomarkers in the CSF with those in brain MRI in conditions found in our clinical practice, and to ascertain the diagnostic accuracy of both techniques used together. Between 2008 and 2009, we included 30 patients with mild cognitive impairment (MCI) who were examined using 1.5 Tesla brain MRI and AD biomarker analysis in CSF. MRI studies were evaluated by 2 radiologists according to the Korf́s visual scale. CSF biomarkers were analysed using INNOTEST reagents for Aβ1-42, total-tau and phospho-tau181p. We evaluated clinical changes 2 years after inclusion. By 2 years after inclusion, 15 of the original 30 patients (50%) had developed AD (NINCDS-ADRA criteria). The predictive utility of AD biomarkers in CSF (RR 2.7; 95% CI, 1.1-6.7; Pde Neurología. Published by Elsevier Espana. All rights reserved.

  9. The Gut-Brain Axis, Including the Microbiome, Leaky Gut and Bacterial Translocation: Mechanisms and Pathophysiological Role in Alzheimer's Disease.

    Science.gov (United States)

    Köhler, Cristiano A; Maes, Michael; Slyepchenko, Anastasiya; Berk, Michael; Solmi, Marco; Lanctôt, Krista L; Carvalho, André F

    2016-01-01

    Alzheimer's disease (AD), the most common form of dementia, is a progressive disorder manifested by gradual memory loss and subsequent impairment in mental and behavioral functions. Though the primary risk factor for AD is advancing age, other factors such as diabetes mellitus, hyperlipidemia, obesity, vascular factors and depression play a role in its pathogenesis. The human gastrointestinal tract has a diverse commensal microbial population, which has bidirectional interactions with the human host that are symbiotic in health, and in addition to nutrition, digestion, plays major roles in inflammation and immunity. The most prevalent hypothesis for AD is the amyloid hypothesis, which states that changes in the proteolytic processing of the amyloid precursor protein leads to the accumulation of the amyloid beta (Aβ) peptide. Aβ then triggers an immune response that drives neuroinflammation and neurodegeneration in AD. The specific role of gut microbiota in modulating neuro-immune functions well beyond the gastrointestinal tract may constitute an important influence on the process of neurodegeneration. We first review the main mechanisms involved in AD physiopathology. Then, we review the alterations in gut microbiota and gut-brain axis that might be relevant to mediate or otherwise affect AD pathogenesis, especially those associated with aging. We finally summarize possible mechanisms that could mediate the involvement of gut-brain axis in AD physiopathology, and propose an integrative model.

  10. Neuroinflammation in Alzheimer's disease wanes with age

    NARCIS (Netherlands)

    Hoozemans, Jeroen J. M.; Rozemuller, Annemieke J. M.; van Haastert, Elise S.; Eikelenboom, Piet; van Gool, Willem A.

    2011-01-01

    Inflammation is a prominent feature in Alzheimer's disease (AD). It has been proposed that aging has an effect on the function of inflammation in the brain, thereby contributing to the development of age-related diseases like AD. However, the age-dependent relationship between inflammation and

  11. Neuroinflammation in Alzheimer's disease wanes with age

    NARCIS (Netherlands)

    Hoozemans, J.J.M.; Rozemuller, A.J.M.; van Haastert, E.S.; Eikelenboom, P.; van Gool, W.A.

    2011-01-01

    ABSTRACT: BACKGROUND: Inflammation is a prominent feature in Alzheimer's disease (AD). It has been proposed that aging has an effect on the function of inflammation in the brain, thereby contributing to the development of age-related diseases like AD. However, the age-dependent relationship between

  12. Alzheimer's disease: synapses gone cold

    Directory of Open Access Journals (Sweden)

    Hyman Bradley T

    2011-08-01

    Full Text Available Abstract Alzheimer's disease (AD is a progressive neurodegenerative disease characterized by insidious cognitive decline and memory dysfunction. Synapse loss is the best pathological correlate of cognitive decline in AD and mounting evidence suggests that AD is primarily a disease of synaptic dysfunction. Soluble oligomeric forms of amyloid beta (Aβ, the peptide that aggregates to form senile plaques in the brain of AD patients, have been shown to be toxic to neuronal synapses both in vitro and in vivo. Aβ oligomers inhibit long-term potentiation (LTP and facilitate long-term depression (LTD, electrophysiological correlates of memory formation. Furthermore, oligomeric Aβ has also been shown to induce synapse loss and cognitive impairment in animals. The molecular underpinnings of these observations are now being elucidated, and may provide clear therapeutic targets for effectively treating the disease. Here, we review recent findings concerning AD pathogenesis with a particular focus on how Aβ impacts synapses.

  13. Cerebrospinal fluid lactate levels and brain [18F]FDG PET hypometabolism within the default mode network in Alzheimer's disease.

    Science.gov (United States)

    Liguori, Claudio; Chiaravalloti, Agostino; Sancesario, Giuseppe; Stefani, Alessandro; Sancesario, Giulia Maria; Mercuri, Nicola Biagio; Schillaci, Orazio; Pierantozzi, Mariangela

    2016-10-01

    It has been suggested that neuronal energy metabolism may be involved in Alzheimer's disease (AD). In this view, the finding of increased cerebrospinal fluid (CSF) lactate levels in AD patients has been considered the result of energetic metabolism dysfunction. Here, we investigated the relationship between neuronal energy metabolism, as measured via CSF lactate levels, and cerebral glucose metabolism, as stated at the 2-deoxy-2-(18F)fluoro-D-glucose positron emission tomography ([18F]FDG PET) in AD patients. AD patients underwent lumbar puncture to measure CSF lactate levels and [18F]FDG PET to assess brain glucose metabolism. CSF and PET data were compared to controls. Since patients were studied at rest, we specifically investigated brain areas active in rest-condition owing to the Default Mode Network (DMN). We correlated the CSF lactate concentrations with the [18F]FDG PET data in brain areas owing to the DMN, using sex, age, disease duration, Mini Mental State Examination, and CSF levels of tau proteins and beta-amyloid as covariates. AD patients (n = 32) showed a significant increase of CSF lactate levels compared to Control 1 group (n = 28). They also showed brain glucose hypometabolism in the DMN areas compared to Control 2 group (n = 30). Within the AD group we found the significant correlation between increased CSF lactate levels and glucose hypometabolism in Broadman areas (BA) owing to left medial prefrontal cortex (BA10, mPFC), left orbitofrontal cortex (BA11, OFC), and left parahippocampal gyrus (BA 35, PHG). We found high CSF levels of lactate and glucose hypometabolism within the DMN in AD patients. Moreover, we found a relationship linking the increased CSF lactate and the reduced glucose consumption in the left mPFC, OFC and PHG, owing to the anterior hub of DMN. These findings could suggest that neural glucose hypometabolism may affect the DMN efficiency in AD, also proposing the possible role of damaged brain energetic machine in

  14. In vivo changes in microglial activation and amyloid deposits in brain regions with hypometabolism in Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Yokokura, Masamichi; Mori, Norio; Yoshihara, Yujiro; Wakuda, Tomoyasu; Takebayashi, Kiyokazu; Iwata, Yasuhide; Nakamura, Kazuhiko [Hamamatsu University School of Medicine, Department of Psychiatry and Neurology, Hamamatsu (Japan); Yagi, Shunsuke; Ouchi, Yasuomi [Hamamatsu University School of Medicine, Laboratory of Human Imaging Research, Molecular Imaging Frontier Research Center, Hamamatsu (Japan); Yoshikawa, Etsuji [Hamamatsu Photonics K.K., Central Research Laboratory, Hamamatsu (Japan); Kikuchi, Mitsuru [Kanazawa University, Department of Psychiatry and Neurobiology, Graduate School of Medical Science, Kanazawa (Japan); Sugihara, Genichi; Suda, Shiro; Tsuchiya, Kenji J.; Suzuki, Katsuaki [Hamamatsu University School of Medicine, Research Center for Child Mental Development, Hamamatsu (Japan); Ueki, Takatoshi [Hamamatsu University School of Medicine, Department of Anatomy, Hamamatsu (Japan)

    2011-02-15

    Amyloid {beta} protein (A{beta}) is known as a pathological substance in Alzheimer's disease (AD) and is assumed to coexist with a degree of activated microglia in the brain. However, it remains unclear whether these two events occur in parallel with characteristic hypometabolism in AD in vivo. The purpose of the present study was to clarify the in vivo relationship between A{beta} accumulation and neuroinflammation in those specific brain regions in early AD. Eleven nootropic drug-naive AD patients underwent a series of positron emission tomography (PET) measurements with [{sup 11}C](R)PK11195, [{sup 11}C]PIB and [{sup 18}F]FDG and a battery of cognitive tests within the same day. The binding potentials (BPs) of [{sup 11}C](R)PK11195 were directly compared with those of [{sup 11}C]PIB in the brain regions with reduced glucose metabolism. BPs of [{sup 11}C](R)PK11195 and [{sup 11}C]PIB were significantly higher in the parietotemporal regions of AD patients than in ten healthy controls. In AD patients, there was a negative correlation between dementia score and [{sup 11}C](R)PK11195 BPs, but not [{sup 11}C]PIB, in the limbic, precuneus and prefrontal regions. Direct comparisons showed a significant negative correlation between [{sup 11}C](R)PK11195 and [{sup 11}C]PIB BPs in the posterior cingulate cortex (PCC) (p < 0.05, corrected) that manifested the most severe reduction in [{sup 18}F]FDG uptake. A lack of coupling between microglial activation and amyloid deposits may indicate that A{beta} accumulation shown by [{sup 11}C]PIB is not always the primary cause of microglial activation, but rather the negative correlation present in the PCC suggests that microglia can show higher activation during the production of A{beta} in early AD. (orig.)

  15. Assessment of brain core temperature using MR DWI-thermometry in Alzheimer disease patients compared to healthy subjects.

    Science.gov (United States)

    Sparacia, Gianvincenzo; Sakai, Koji; Yamada, Kei; Giordano, Giovanna; Coppola, Rosalia; Midiri, Massimo; Grimaldi, Luigi Maria

    2017-04-01

    To assess the brain core temperature of Alzheimer disease (AD) patients in comparison with healthy volunteers using diffusion-weighted thermometry. Fourteen AD patients (3 men, 11 women; age range 60-81 years, mean age 73.8 ± 6.1 years) and 14 healthy volunteers, age and sex-matched (mean age 70.1 ± 6.9 years; range 62-84 years; 5 men, 9 women) underwent MR examination between February 2014 and March 2016. MR imaging studies were performed with a 1.5-T MR scanner. Brain core temperature (T: °C) was calculated using the following equation from the diffusion coefficient (D) in the lateral ventricular (LV) cerebrospinal fluid: T = 2256.74/ln (4.39221/D) - 273.15 using a standard DWI single-shot echo-planar pulse sequence (b value 1000 s/mm 2 ). Statistical analysis was performed using a nonparametric Wilcoxon rank-sum test to compare the patient and control groups regarding LV temperatures. There was no significant difference (P = 0.1937) in LV temperature between patients (mean 37.9 ± 1.1 °C, range 35.8-39.2 °C) and control group (38.7 ± 1.4 °C, range 36.9-42.7 °C). Brain core temperature in AD patients showed no significant alterations compared to healthy volunteers.

  16. Increased expression of the remodeling- and tumorigenic-associated factor osteopontin in pyramidal neurons of the Alzheimer's disease brain.

    Science.gov (United States)

    Wung, John K; Perry, George; Kowalski, Aaron; Harris, Peggy L R; Bishop, Glenda M; Trivedi, Mehul A; Johnson, Sterling C; Smith, Mark A; Denhardt, David T; Atwood, Craig S

    2007-02-01

    Osteopontin (OPN) is a glycophosphoprotein expressed by several cell types and has pro-adhesive, chemotactic, and cytokine-like properties. OPN is involved in a number of physiologic and pathologic events including angiogenesis, apoptosis, inflammation, oxidative stress, remyelination, wound healing, bone remodeling, cell migration and tumorigenesis. Since these functions of OPN, and the events that it regulates, are involved with neurodegeneration, we examined whether OPN was differentially expressed in the hippocampus of the Alzheimer's disease (AD) compared with age-matched (59-93 years) control brain. We report for the first time the immunocytochemical localization of OPN in the cytoplasm of pyramidal neurons. In AD brains, there was a significant 41 % increase in the expression of neuron OPN compared with age-matched control brain. No staining of other neuronal cell types was observed. Additionally, there was a significant positive correlation between OPN staining intensity and both amyloid-beta load (r(2) = 0.25; P < 0.05; n = 20) and aging (r(2) = 0.32; P < 0.01; n = 20) among all control and AD subjects. Controlling for age indicated that OPN expression was significantly influenced by amyloid-beta load, but not age. While the functional consequences of this amyloid-beta associated increase in OPN expression are unclear, it is notable that OPN is primarily localized to those neurons that are known to be vulnerable to AD-related neurite loss, degeneration and death. Given that the induction of OPN expression (and amyloid-beta generation) is associated with remodeling and tumorigenesis, our results suggest that OPN may play a role in the aberrant re-entry of neurons into the cell cycle and/or neuronal remyelination in AD.

  17. Neurochemical Characterization of PSA-NCAM+ Cells in the Human Brain and Phenotypic Quantification in Alzheimer's Disease Entorhinal Cortex.

    Science.gov (United States)

    Murray, Helen C; Swanson, Molly E V; Dieriks, B Victor; Turner, Clinton; Faull, Richard L M; Curtis, Maurice A

    2018-02-21

    Polysialylated neural cell adhesion molecule (PSA-NCAM) is widely expressed in the adult human brain and facilitates structural remodeling of cells through steric inhibition of intercellular NCAM adhesion. We previously showed that PSA-NCAM immunoreactivity is decreased in the entorhinal cortex in Alzheimer's disease (AD). Based on available evidence, we hypothesized that a loss of PSA-NCAM + interneurons may underlie this reduction. PSA-NCAM expression by interneurons has previously been described in the human medial prefrontal cortex. Here we used postmortem human brain tissue to provide further evidence of PSA-NCAM + interneurons throughout the human hippocampal formation and additional cortical regions. Furthermore, PSA-NCAM + cell populations were assessed in the entorhinal cortex of normal and AD cases using fluorescent double labeling and manual cell counting. We found a significant decrease in the number of PSA-NCAM + cells per mm 2 in layer II and V of the entorhinal cortex, supporting our previous description of reduced PSA-NCAM immunoreactivity. Additionally, we found a significant decrease in the proportion of PSA-NCAM + cells that co-labeled with NeuN and parvalbumin, but no change in the proportion that co-labeled with calbindin or calretinin. These results demonstrate that PSA-NCAM is expressed by a variety of interneuron populations throughout the brain. Furthermore, that loss of PSA-NCAM expression by NeuN + cells predominantly contributes to the reduced PSA-NCAM immunoreactivity in the AD entorhinal cortex. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. Early Brain Response to Low-Dose Radiation Exposure Involves Molecular Networks and Pathways Associated with Cognitive Functions, Advanced Aging and Alzheimer's Disease

    Energy Technology Data Exchange (ETDEWEB)

    Lowe, Xiu R; Bhattacharya, Sanchita; Marchetti, Francesco; Wyrobek, Andrew J.

    2008-06-06

    Understanding the cognitive and behavioral consequences of brain exposures to low-dose ionizing radiation has broad relevance for health risks from medical radiation diagnostic procedures, radiotherapy, environmental nuclear contamination, as well as earth orbit and space missions. Analyses of transcriptome profiles of murine brain tissue after whole-body radiation showed that low-dose exposures (10 cGy) induced genes not affected by high dose (2 Gy), and low-dose genes were associated with unique pathways and functions. The low-dose response had two major components: pathways that are consistently seen across tissues, and pathways that were brain tissue specific. Low-dose genes clustered into a saturated network (p < 10{sup -53}) containing mostly down-regulated genes involving ion channels, long-term potentiation and depression, vascular damage, etc. We identified 9 neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue after low-dose radiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer's disease. Mice exposed to high-dose radiation did not show these effects and associations. Our findings indicate that the molecular response of the mouse brain within a few hours after low-dose irradiation involves the down-regulation of neural pathways associated with cognitive dysfunctions that are also down regulated in normal human aging and Alzheimer's disease.

  19. Early Brain Response to Low-Dose Radiation Exposure Involves Molecular Networks and Pathways Associated with Cognitive Functions, Advanced Aging and Alzheimer's Disease

    International Nuclear Information System (INIS)

    Lowe, Xiu R.; Bhattacharya, Sanchita; Marchetti, Francesco; Wyrobek, Andrew J.

    2008-01-01

    Understanding the cognitive and behavioral consequences of brain exposures to low-dose ionizing radiation has broad relevance for health risks from medical radiation diagnostic procedures, radiotherapy, environmental nuclear contamination, as well as earth orbit and space missions. Analyses of transcriptome profiles of murine brain tissue after whole-body radiation showed that low-dose exposures (10 cGy) induced genes not affected by high dose (2 Gy), and low-dose genes were associated with unique pathways and functions. The low-dose response had two major components: pathways that are consistently seen across tissues, and pathways that were brain tissue specific. Low-dose genes clustered into a saturated network (p -53 ) containing mostly down-regulated genes involving ion channels, long-term potentiation and depression, vascular damage, etc. We identified 9 neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue after low-dose radiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer's disease. Mice exposed to high-dose radiation did not show these effects and associations. Our findings indicate that the molecular response of the mouse brain within a few hours after low-dose irradiation involves the down-regulation of neural pathways associated with cognitive dysfunctions that are also down regulated in normal human aging and Alzheimer's disease

  20. APP processing in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Zhang Yun-wu

    2011-01-01

    Full Text Available Abstract An important pathological feature of Alzheimer's disease (AD is the presence of extracellular senile plaques in the brain. Senile plaques are composed of aggregations of small peptides called β-amyloid (Aβ. Multiple lines of evidence demonstrate that overproduction/aggregation of Aβ in the brain is a primary cause of AD and inhibition of Aβ generation has become a hot topic in AD research. Aβ is generated from β-amyloid precursor protein (APP through sequential cleavages first by β-secretase and then by γ-secretase complex. Alternatively, APP can be cleaved by α-secretase within the Aβ domain to release soluble APPα and preclude Aβ generation. Cleavage of APP by caspases may also contribute to AD pathologies. Therefore, understanding the metabolism/processing of APP is crucial for AD therapeutics. Here we review current knowledge of APP processing regulation as well as the patho/physiological functions of APP and its metabolites.

  1. The pilot European Alzheimer's Disease Neuroimaging Initiative of the European Alzheimer's Disease Consortium

    DEFF Research Database (Denmark)

    Frisoni, G.B.; Henneman, W.J.; Weiner, M.W.

    2008-01-01

    BACKGROUND: In North America, the Alzheimer's Disease Neuroimaging Initiative (ADNI) has established a platform to track the brain changes of Alzheimer's disease. A pilot study has been carried out in Europe to test the feasibility of the adoption of the ADNI platform (pilot E-ADNI). METHODS: Seven...... academic sites of the European Alzheimer's Disease Consortium (EADC) enrolled 19 patients with mild cognitive impairment (MCI), 22 with AD, and 18 older healthy persons by using the ADNI clinical and neuropsychological battery. ADNI compliant magnetic resonance imaging (MRI) scans, cerebrospinal fluid...

  2. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... which Alzheimer's disease is placed in the same category as other chronic diseases, such as ... report contains data on the impact of this disease in every state across the ...

  3. Neuroinflammation and Alzheimer disease: clinical and therapeutic implications

    NARCIS (Netherlands)

    Eikelenboom, P.; Rozemuller, A. J.; Hoozemans, J. J.; Veerhuis, R.; van Gool, W. A.

    2000-01-01

    In Alzheimer disease brains, the amyloid plaques are closely associated with a locally induced, nonimmune-mediated, chronic inflammatory response without any apparent influx of leukocytes from the blood. The present findings indicate that in cerebral A beta diseases (Alzheimer disease, Down

  4. Brain Insulin Signaling and Alzheimer's Disease: Current Evidence and Future Directions

    OpenAIRE

    Schiöth, Helgi B.; Craft, Suzanne; Brooks, Samantha J.; Frey, William H.; Benedict, Christian

    2011-01-01

    Insulin receptors in the brain are found in high densities in the hippocampus, a region that is fundamentally involved in the acquisition, consolidation, and recollection of new information. Using the intranasal method, which effectively bypasses the blood–brain barrier to deliver and target insulin directly from the nose to the brain, a series of experiments involving healthy humans has shown that increased central nervous system (CNS) insulin action enhances learning and memory processes as...

  5. Apathy and white matter integrity in Alzheimer's disease: a whole brain analysis with tract-based spatial statistics.

    Directory of Open Access Journals (Sweden)

    Changtae Hahn

    Full Text Available The aim of this study was to investigate the microstructural alterations of white matter (WM in Alzheimer's disease (AD patients with apathy and to observe the relationships with the severity of apathy. Sixty drug-naïve subjects took part in this study (30 apathetic and 30 nonapathetic subjects with AD. The loss of integrity in WM was compared in AD patients with and without apathy through measurement of fractional anisotropy (FA using by tract-based spatial statistics (TBSS. In addition, we explored the correlation pattern between FA values and the severity of apathy in AD patients with apathy. The apathy group had significantly reduced FA values (p(corrected<0.05 in the genu of the corpus callosum compared to the nonapathy group. The severity of apathy was negatively correlated with FA values of the left anterior and posterior cingulum, right superior longitudinal fasciculus, splenium, body and genu of the corpus callosum and bilateral uncinate fasciculusin the apathy group (p(corrected<0.05. This study was the first to explore FA values in whole brain WM in AD patients with apathy. The findings of these microstructural alterations of WM may be the key to the understanding of underlying neurobiological mechanism and clinical significances of apathy in AD.

  6. Selegiline for Alzheimer's disease.

    Science.gov (United States)

    Birks, J; Flicker, L

    2003-01-01

    Alzheimer's disease is the most common cause of dementia in older people accounting for some 60% of cases with late-onset cognitive deterioration. It is now thought that several neurotransmitter dysfunctions are involved from an early stage in the pathogenesis of Alzheimer's disease-associated cognitive decline. The efficacy of selegiline for symptoms of Alzheimer's disease remains controversial and is reflected by its low rate of prescription and the lack of approval by several regulatory authorities in Europe and elsewhere. Reasons for this uncertainty involve the modest overall effects observed in some trials, the lack of benefit observed in several trials, the use of cross-over designs which harbour methodological problems in a disease like dementia and the difficulty in interpreting results from trials when a variety of measurement scales are used to assess outcomes. The objective of this review is to assess whether or not selegiline improves the well-being of patients with Alzheimer's disease. The Cochrane Dementia and Cognitive Impairment Group Register of Clinical Trials, was searched using the terms 'selegiline', 'l-deprenyl', "eldepryl" and "monamine oxidase inhibitor-B". MEDLINE, PsycLIT and EMBASE electronic databases were searched with the above terms in addition to using the group strategy (see group details) to limit the searches to randomised controlled trials. All unconfounded, double-blind, randomised controlled trials in which treatment with selegiline was administered for more than a day and compared to placebo in patients with dementia. An individual patient data meta-analysis of selegiline, Wilcock 2002 provides much of the data that are available for this review. Seven studies provided individual patient data and this was pooled with summary statistics from the published papers of the other nine studies. Where possible, intention-to-treat data were used but usually the meta analyses were restricted to completers' data (data on people who

  7. and late onset Alzheimer's disease

    African Journals Online (AJOL)

    Yomi

    2012-03-15

    Mar 15, 2012 ... Alzheimer's disease (AD) is a prevalent disorder and the most common cause of dementia in elderly populations. Genetic and environmental factors together play a role in developing late onset. Alzheimer's disease (LOAD). According to the recent published papers, ACE is one of the candidate.

  8. Molecular subtypes of Alzheimer's disease.

    Science.gov (United States)

    Di Fede, Giuseppe; Catania, Marcella; Maderna, Emanuela; Ghidoni, Roberta; Benussi, Luisa; Tonoli, Elisa; Giaccone, Giorgio; Moda, Fabio; Paterlini, Anna; Campagnani, Ilaria; Sorrentino, Stefano; Colombo, Laura; Kubis, Adriana; Bistaffa, Edoardo; Ghetti, Bernardino; Tagliavini, Fabrizio

    2018-02-19

    Protein misfolding and aggregation is a central feature of several neurodegenerative disorders including Alzheimer's disease (AD), in which assemblies of amyloid β (Aβ) peptides accumulate in the brain in the form of parenchymal and/or vascular amyloid. A widely accepted concept is that AD is characterized by distinct clinical and neuropathological phenotypes. Recent studies revealed that Aβ assemblies might have structural differences among AD brains and that such pleomorphic assemblies can correlate with distinct disease phenotypes. We found that in both sporadic and inherited forms of AD, amyloid aggregates differ in the biochemical composition of Aβ species. These differences affect the physicochemical properties of Aβ assemblies including aggregation kinetics, resistance to degradation by proteases and seeding ability. Aβ-amyloidosis can be induced and propagated in animal models by inoculation of brain extracts containing aggregated Aβ. We found that brain homogenates from AD patients with different molecular profiles of Aβ are able to induce distinct patterns of Aβ-amyloidosis when injected into mice. Overall these data suggest that the assembly of mixtures of Aβ peptides into different Aβ seeds leads to the formation of distinct subtypes of amyloid having distinctive physicochemical and biological properties which result in the generation of distinct AD molecular subgroups.

  9. Theobromine-Induced Changes in A1 Purinergic Receptor Gene Expression and Distribution in a Rat Brain Alzheimer's Disease Model.

    Science.gov (United States)

    Mendiola-Precoma, Jesus; Padilla, Karla; Rodríguez-Cruz, Alfredo; Berumen, Laura C; Miledi, Ricardo; García-Alcocer, Guadalupe

    2017-01-01

    Dementia caused by Alzheimer's disease (AD) is mainly characterized by accumulation in the brain of extra- and intraneuronal amyloid-β (Aβ) and tau proteins, respectively, which selectively affect specific regions, particularly the neocortex and the hippocampus. Sporadic AD is mainly caused by an increase in apolipoprotein E, a component of chylomicrons, which are cholesterol transporters in the brain. Recent studies have shown that high lipid levels, especially cholesterol, are linked to AD. Adenosine is an atypical neurotransmitter that regulates a wide range of physiological functions by activating four P1 receptors (A1, A2A, A2B, and A3) and P2 purinergic receptors that are G protein-coupled. A1 receptors are involved in the inhibition of neurotransmitter release, which could be related to AD. The aim of the present work was to study the effects of a lard-enriched diet (LED) on cognitive and memory processes in adult rats (6 months of age) as well as the effect of theobromine on these processes. The results indicated that the fat-enriched diet resulted in a long-term deterioration in cognitive and memory functions. Increased levels of Aβ protein and IL-1β were also observed in the rats fed with a high-cholesterol diet, which were used to validate the AD animal model. In addition, the results of qPCR and immunohistochemistry indicated a decrease in gene expression and distribution of A1 purinegic receptor, respectively, in the hippocampus of LED-fed rats. Interestingly, theobromine, at both concentrations tested, restored A1 receptor levels and improved cognitive functions and Aβ levels for a dose of 30 mg/L drinking water.

  10. Diagnostic value of β amyloid plaques imaging agent 131I-IMPY brain imaging in early Alzheimer's disease

    International Nuclear Information System (INIS)

    Ye Wanzhong; Lu Chunxiong; Yang Min; Bao Jiandong; Cheng Zhaohuo; Cai Deliang; Wang Zhiqiang; Yang Bixiu

    2012-01-01

    Objective: To evaluate the diagnostic value of β-amyloid plaques imaging agent [ 131 I] 2( 4-dimethylaminop henyl)-6-iodoimidazo [1, 2-α] pyridine ( 131 I-IMPY) SPECT imaging in early Alzheimer's Disease. Methods: 24 cases of AD (7 males, 17 females, aged 48∼79 years) and 14 normal (6 males, 8 females, aged 42∼67 years) control subjects were selected for this study. 131 I-IMPY SPECT imaging was carried out 2-3 h post injection. 131 I-IMPY uptake defined as the ratio of each brain gyrus and cerebellum uptake on fixed region of interest (ROI) (Rcl/cb) was calculated. Comparative analysis between the two groups was carried out using t-test. Results: In patients with early AD (MCI), 131 I-IMPY was increased in parietal gyrus, temporal gyrus and frontal gyrus compared with normal control group and it were found to be statistically significant (t = 1.3967∼2.8757, all P 0.05). In patients with AD, increase in 131 I-IMPY were observed in parietal, temporal, occipital lobes and basal ganglia compared with normal control group and it were found to be statistically significant (t=2.1001∼6.2789, all P 0.05), and 131 I-IMPY was increased in occipital lobes and basal ganglia compared with MCI group and it were found to be statistically significant (t=2.0850∼3.6772, all P 131 I-IMPY was lightly increased in each brain of left side gyrus compared with right but without statistically significant difference (t=0.1273∼0.5571, all P>0.05). Conclusions: 131 I-IMPY SPECT Imaging was helpful for early diagnosis of AD. (authors)

  11. How Alzheimer's Changes the Brain

    Medline Plus

    Full Text Available ... 4-minute video shows how Alzheimer’s affects the human brain and looks at promising ideas to treat and prevent the disease. Category Science & ... The resistant brain: nourishing our bodies against Alzheimer’s | Owen Carmichael | TEDxLSU - Duration: 12:17. ...

  12. Proteomic profiling of brain cortex tissues in a Tau transgenic mouse model of Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Seong-Hun; Jung, In-Soo; Han, Gi-Yeon; Kim, Nam-Hee; Kim, Hyun-Jung [School of Life Sciences and Biotechnology, Korea University, Seoul 136-701 (Korea, Republic of); Kim, Chan-Wha, E-mail: cwkim@korea.ac.kr [School of Life Sciences and Biotechnology, Korea University, Seoul 136-701 (Korea, Republic of)

    2013-01-11

    Highlights: Black-Right-Pointing-Pointer A transgenic mouse model expressing NSE-htau23 was used. Black-Right-Pointing-Pointer 2D-gel electrophoresis to analyze the cortex proteins of transgenic mice was used. Black-Right-Pointing-Pointer Differentially expressed spots in different stages of AD were identified. Black-Right-Pointing-Pointer GSTP1 and CAII were downregulated with the progression of AD. Black-Right-Pointing-Pointer SCRN1 and ATP6VE1 were up regulated and down regulated differentially. -- Abstract: Alzheimer's disease (AD) involves regionalized neuronal death, synaptic loss, and an accumulation of intracellular neurofibrillary tangles and extracellular senile plaques. Although there have been numerous studies on tau proteins and AD in various stages of neurodegenerative disease pathology, the relationship between tau and AD is not yet fully understood. A transgenic mouse model expressing neuron-specific enolase (NSE)-controlled human wild-type tau (NSE-htau23), which displays some of the typical Alzheimer-associated pathological features, was used to analyze the brain proteome associated with tau tangle deposition. Two-dimensional electrophoresis was performed to compare the cortex proteins of transgenic mice (6- and 12-month-old) with those of control mice. Differentially expressed spots in different stages of AD were identified with ESI-Q-TOF (electrospray ionization quadruple time-of-flight) mass spectrometry and liquid chromatography/tandem mass spectrometry. Among the identified proteins, glutathione S-transferase P 1 (GSTP1) and carbonic anhydrase II (CAII) were down-regulated with the progression of AD, and secerin-1 (SCRN1) and V-type proton ATPase subunit E 1 (ATP6VE1) were up-regulated only in the early stages, and down-regulated in the later stages of AD. The proteins, which were further confirmed by RT-PCR at the mRNA level and with western blotting at the protein level, are expected to be good candidates as drug targets for AD. The

  13. Longitudinal brain metabolic changes from amnestic mild cognitive impairment to Alzheimer's disease

    Science.gov (United States)

    Fouquet, Marine; Desgranges, Béatrice; Landeau, Brigitte; Duchesnay, Edouard; Mézenge, Florence; De La Sayette, Vincent; Viader, Fausto; Baron, Jean-Claude; Eustache, Francis; Chételat, Gaël

    2009-01-01

    A sensitive marker for monitoring progression of early Alzheimer’s Disease (AD) would help to develop and test new therapeutic strategies. The present study aimed at investigating brain metabolism changes over time, as potential monitoring marker, in patients with amnestic Mild Cognitive Impairment (aMCI), according to their clinical outcome (converters or non-converters), and in relation to their cognitive decline. Seventeen aMCI patients underwent MRI and 18FDG-PET scans both at inclusion and 18 months later. Baseline and follow-up PET data were corrected for partial volume effects and spatially normalized using MRI data, scaled to the vermis and compared using SPM2. ‘PET-PAC’ maps reflecting metabolic percent annual changes were created for correlation analyses with cognitive decline. In the whole sample, the greatest metabolic decrease concerned the posterior cingulate-precuneus area. Converters had significantly greater metabolic decrease than nonconverters in two ventro-medial prefrontal areas, the subgenual (BA25) and anterior cingulate (BA24/32). PET-PAC in BA25 and BA24/32 combined allowed complete between-group discrimination. BA25 PET-PAC significantly correlated with both cognitive decline and PET-PAC in the hippocampal region and temporal pole, while BA24/32 PET-PAC correlated with posterior cingulate PET-PAC. Finally, the metabolic change in BA8/9/10 was inversely related to that in BA25 and showed relative increase with cognitive decline, suggesting that compensatory processes may occur in this dorso-medial prefrontal region. The observed ventro-medial prefrontal disruption is likely to reflect disconnection from the hippocampus, both indirectly through the cingulum bundle and posterior cingulate cortex for BA24/32, and directly through the uncinate fasciculus for BA25. Altogether, our findings emphasize the potential of 18FDG-PET for monitoring early AD progression. PMID:19477964

  14. How Alzheimer's Changes the Brain

    Medline Plus

    Full Text Available ... 4-minute video shows how Alzheimer’s affects the human brain and looks at promising ideas to treat and prevent the disease. Category Science & Technology License Standard YouTube License Show ...

  15. How Alzheimer's Changes the Brain

    Medline Plus

    Full Text Available ... minute video shows how Alzheimer’s affects the human brain and looks at promising ideas to treat and prevent the disease. Category Science & Technology License Standard YouTube License Show more Show less ...

  16. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... home care. Take action. Become an advocate SPECIAL REPORT: FINANCIAL AND PERSONAL BENEFITS OF EARLY DIAGNOSIS Early ... State The 2018 Alzheimer's Disease Facts and Figures report contains data on the impact of this disease ...

  17. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... disease is the only top 10 cause of death in the United States that cannot be prevented, ... Alzheimer's disease is the sixth-leading cause of death in the United States, and the fifth-leading ...

  18. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... disease are no longer consistent with the scientific evidence, and no longer serve our health care needs. ... irrevocable disability occurs. LEARN ABOUT OUR COMMITMENT TO RESEARCH. Read More Alzheimer's Disease Facts in Each State ...

  19. Integrative Understanding of Emergent Brain Properties, Quantum Brain Hypotheses, and Connectome Alterations in Dementia are Key Challenges to Conquer Alzheimer's Disease.

    Science.gov (United States)

    Kuljiš, Rodrigo O

    2010-01-01

    The biological substrate for cognition remains a challenge as much as defining this function of living beings. Here, we examine some of the difficulties to understand normal and disordered cognition in humans. We use aspects of Alzheimer's disease and related disorders to illustrate how the wealth of information at many conceptually separate, even intellectually decoupled, physical scales - in particular at the Molecular Neuroscience versus Systems Neuroscience/Neuropsychology levels - presents a challenge in terms of true interdisciplinary integration towards a coherent understanding. These unresolved dilemmas include critically the as yet untested quantum brain hypothesis, and the embryonic attempts to develop and define the so-called connectome in humans and in non-human models of disease. To mitigate these challenges, we propose a scheme incorporating the vast array of scales of the space and time (space-time) manifold from at least the subatomic through cognitive-behavioral dimensions of inquiry, to achieve a new understanding of both normal and disordered cognition, that is essential for a new era of progress in the Generative Sciences and its application to translational efforts for disease prevention and treatment.

  20. Brain glucose metabolism in the early and specific diagnosis of Alzheimer's disease. FDG-PET studies in MCI and AD

    International Nuclear Information System (INIS)

    Mosconi, Lisa

    2005-01-01

    The demographics of aging suggest a great need for the early diagnosis of dementia and the development of preventive strategies. Neuropathology and structural MRI studies have pointed to the medial temporal lobe (MTL) as the brain region earliest affected in Alzheimer's disease (AD). MRI findings provide strong evidence that in mild cognitive impairments (MCI), AD-related volume losses can be reproducibly detected in the hippocampus, the entorhinal cortex (EC) and, to a lesser extent, the parahippocampal gyrus; they also indicate that lateral temporal lobe changes are becoming increasingly useful in predicting the transition to dementia. Fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) imaging has revealed glucose metabolic reductions in the parieto-temporal, frontal and posterior cingulate cortices to be the hallmark of AD. Overall, the pattern of cortical metabolic changes has been useful for the prediction of future AD as well as in distinguishing AD from other neurodegenerative diseases. FDG-PET on average achieves 90% sensitivity in identifying AD, although specificity in differentiating AD from other dementias is lower. Moreover, recent MRI-guided FDG-PET studies have shown that MTL hypometabolism is the most specific and sensitive measure for the identification of MCI, while the utility of cortical deficits is controversial. This review highlights cross-sectional, prediction and longitudinal FDG-PET studies and attempts to put into perspective the value of FDG-PET in diagnosing AD-like changes, particularly at an early stage, and in providing diagnostic specificity. The examination of MTL structures, which has so far been exclusive to MRI protocols, is then examined as a possible strategy to improve diagnostic specificity. All told, there is considerable promise that early and specific diagnosis is feasible through a combination of imaging modalities. (orig.)

  1. Role of physical exercise in Alzheimer's disease

    OpenAIRE

    CHEN, WEI-WEI; ZHANG, XIA; HUANG, WEN-JUAN

    2016-01-01

    The benefits of physical exercise on the brain and general wellness are well recognised, but not particularly well known to the general public. Understanding the importance of integrating active behavior for overall health is crucial at any age and particularly for the elderly who are at risk of developing Alzheimer's disease (AD), a disease mainly affecting individuals aged >65 years. AD is a neurodegenerative disease characterized by extracellular senile plaques of amyloid-?, intracellular ...

  2. [Prevention and treatment of Alzheimer disease].

    Science.gov (United States)

    Donoso S, Archibaldo; Delgado D, Carolina

    2009-02-01

    The pharmacological interventions for Alzheimer disease should be based in its pathogenic mechanisms such as amyloidogenesis, tau hyperphosphorilation, disturbances in neurotransmission and changes in neuronal trophism. Other therapies derive from epidemiological observations, such as antioxidants and anti-inflammatory drugs, estrogens, statins and anti hypertensive drugs. Some life style interventions, such as changes in diet, exercise and brain stimulation could also be beneficial for the prevention of Alzheimer disease. Ongoing research on pathogenic mechanisms promises the discovery of more effective therapies. Healthy life style should always be recommended due to its benefit and lack of untoward effects.

  3. Patterns of regional brain hypometabolism associated with knowledge of semantic features and categories in alzheimer's disease

    DEFF Research Database (Denmark)

    Zahn, R.; Garrard, P.; Talazko, J.

    2006-01-01

    damage to distributed representations within nonspecialized brain areas. To our knowledge, there have been no direct correlations of neuroimaging of in vivo brain function in AD with performance on tasks differentially addressing visual and functional knowledge of living and nonliving concepts. We used...... properties of nonliving objects. Visual property verification of living objects was significantly correlated with left posterior fusiform gyrus metabolism (Brodmann's area [BA] 37/19). Effects of visual and functional property verification for nonliving objects largely overlapped in the left anterior...

  4. Providing Counseling for Individuals with Alzheimer's Disease and Their Caregivers

    Science.gov (United States)

    Granello, Paul F.; Fleming, Matthew S.

    2008-01-01

    Alzheimer's disease is a progressive condition that results in brain wasting and eventual death. With its increasing diagnosis rate, counselors will likely acquire clients with Alzheimer's disease or their caregivers. Important background information and several practical counseling methods are provided that may assist counselors working with this…

  5. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... estimated 5.5 million Americans of all ages have Alzheimer's disease. Of the estimated 5.5 million ... 200,000 individuals are under age 65 and have younger-onset Alzheimer's. One in 10 people age ...

  6. Alzheimer disease: Quantitative analysis of I-123-iodoamphetamine SPECT brain imaging

    International Nuclear Information System (INIS)

    Hellman, R.S.; Tikofsky, R.S.; Collier, B.D.; Hoffmann, R.G.; Palmer, D.W.; Glatt, S.L.; Antuono, P.G.; Isitman, A.T.; Papke, R.A.

    1989-01-01

    To enable a more quantitative diagnosis of senile dementia of the Alzheimer type (SDAT), the authors developed and tested a semiautomated method to define regions of interest (ROIs) to be used in quantitating results from single photon emission computed tomography (SPECT) of regional cerebral blood flow performed with N-isopropyl iodine-123-iodoamphetamine. SPECT/IMP imaging was performed in ten patients with probable SDAT and seven healthy subjects. Multiple ROIs were manually and semiautomatically generated, and uptake was quantitated for each ROI. Mean cortical activity was estimated as the average of the mean activity in 24 semiautomatically generated ROIs; mean cerebellar activity was determined from the mean activity in separate ROIs. A ratio of parietal to cerebellar activity less than 0.60 and a ratio of parietal to mean cortical activity less than 0.90 allowed correct categorization of nine of ten and eight of ten patients, respectively, with SDAT and all control subjects. The degree of diminished mental status observed in patients with SDAT correlated with both global and regional changes in IMP uptake

  7. Alzheimer's Disease: The Death of the Disease.

    Science.gov (United States)

    McBroom, Lynn W.

    1987-01-01

    Alzheimer's disease, a form of dementia in middle-age and older adults is becoming more evident because of growing numbers of older people and better diagnosis and detection methods. Describes the behavioral and physical symptoms of the disease as well as specific suggestions for care of patients with Alzheimer's disease, including dealing with…

  8. Neurogenesis and Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Philippe Taupin

    2006-01-01

    Full Text Available Alzheimer’s disease (AD is a neurodegenerative disease, characterized in the brain by amyloid plaque deposits and neurofibrillary tangles. It is the most common form of dementia among older people. There is at present no cure for AD, and current treatments consist mainly in drug therapy. Potential therapies for AD involve gene and cellular therapy. The recent confirmation that neurogenesis occurs in the adult brain and neural stem cells (NSCs reside in the adult central nervous system (CNS provide new opportunities for cellular therapy in the CNS, particularly for AD, and to better understand brain physiopathology. Hence, researchers have aimed at characterizing neurogenesis in patients with AD. Studies show that neurogenesis is increased in these patients, and in animal models of AD. The effect of drugs used to treat AD on neurogenesis is currently being investigated, to identify whether neurogenesis contributes to their therapeutic activities.

  9. Galantamine for Alzheimer's disease.

    Science.gov (United States)

    Olin, J; Schneider, L

    2001-01-01

    Galantamine (also called galanthamine, marketed as Reminyl (Janssen)) can be isolated from several plants, including daffodil bulbs, and now synthesized. Galantamine is a specific, competitive, and reversible acetylcholinesterase inhibitor. It is also an allosteric modulator at nicotinic cholinergic receptor sites potentiating cholinergic nicotinic neurotransmission. A small number of early studies showed mild cognitive and global benefits for patients with Alzheimer's disease, and recently several multicentre clinical trials have been published with positive findings. Galantamine has received regulatory approval in Sweden, is available in Austria, and awaits marketing approval in the United States, Europe, and other countries. The objective of this review is to assess the clinical effects of galantamine in patients with probable Alzheimer's disease, and to investigate potential moderators of an effect. The Cochrane Dementia Group specialized register of clinical trials was searched using the terms 'galantamine,' and 'galanthamine' (15 February 2000) as was the Cochrane Controlled Trials Register (2000, Issue 2). These terms were also used to search the following databases: EMBASE, MEDLINE, PsychLit; Combined Health Information Database, NRR (National Research Register), ADEAR (Alzheimer's Disease Education and Referral Centre clinical database, BIOMED (Biomedicine and Health), Glaxo-Wellcome Clinical Trials Register, National Institutes of Health Clinical Trials Databases, Current Controlled Trials, Dissertation Abstracts (mainly North American dissertations) 1961-1994, Index to UK Theses (British dissertations) 1970-1994. Published reviews were inspected for further sources. Additional information was collected from an unpublished investigational brochure for galantamine. Trials selected were randomized, double-blind, parallel-group, and unconfounded comparisons of galantamine with placebo for a treatment duration of greater than 4 weeks in people with Alzheimer

  10. Advancing frontiers in Alzheimer's disease research

    International Nuclear Information System (INIS)

    Glenner, G.G.; Wurtman, R.J.

    1987-01-01

    This book contain 16 chapters. Some of the titles are: Transmitter Alterations in Alzheimer's Disease: Relation to Cortical Dysfunction as Suggested by Positron Emission Tomography; Single-Photon Emission Computed Tomography in the Clinical Evaluation of Dementia; Clinical Diagnosis of Alzheimer's Disease; Down's Syndrome and Alzheimer's Disease: What is the Relationship; and Beta Protein: A Possible Marker for Alzheimer's Disease

  11. Functional brain SPECT with 99mTc-HMPAO in the diagnosis of Alzheimer disease

    International Nuclear Information System (INIS)

    Urbanek, J.; Kupka, K.; Samal, M.; Jirak, R.; Obenberger, J.

    1998-01-01

    The explanatory power of perfusion diagrams obtained by the title technique was examined. In addition to the standard reconstruction procedure, a special reorientation procedure aimed at a differentiation of the hippocampus structure was applied. The study gave evidence of a high specificity and sensitivity of brain SPECT in the differential diagnosis of dementias. Multifactorial analysis of all available diagnostic techniques has borne out the dominant position of brain SPECT with 99m Tc-HMPAO, particularly when using special projection onto the hippocampus, and has led to the formulation of an examination algorithm where a combination of SPECT and MRI (and CT) enables DAT to be distinguished from dementias of other etiologies with a probability higher than 90%

  12. Tau Processing by Mural Cells in Traumatic Brain Injury and Alzheimer’s Disease

    Science.gov (United States)

    2017-10-01

    Henkel JS, Appel SH and Zlokovic BV. Blood- spinal cord barrier breakdown and pericyte reductions in amyotrophic lateral sclerosis. Acta Neuropathol 125...TBI (r-mTBI) and determine the contribution of these cells to the tau pathology associated with head trauma . Consistent with other neurodegenerative...in mural cell expression and functional tau processing in the context of brain trauma . Furthermore, mural cell expression is reduced in Alzheimer’s

  13. A computed tomography study of Alzheimer's disease

    International Nuclear Information System (INIS)

    Arai, H.; Kobayashi, K.; Juntendo Univ. School of Medicine, Tokyo; Ikeda, Y.; Nagao, Y.; Ogihara, R.; Kosaka, K.; Psychiatric Research Inst. of Tokyo

    1983-01-01

    Computed tomography (CT) was used to study cerebral atrophy in 18 patients with clinically diagnosed Alzheimer's disease of presenile type and in 14 healthy age-matched subjects as controls. Using the computerized planimetric method, Subarachnoid Space Volume Index and Ventricle Volume Index were calculated as the measure of cortical atrophy and ventricular dilatation respectively. From the results the following conclusions were drawn: 1. The cerebral atrophy in Alzheimer patients could be attributable to the disease processes rather than to physiological aging of the brain. 2. The degree of atrophy increases in parallel with the progress of the clinical stage, and the cortical atrophy is already apparent at an early stage, whereas the ventricular dilatation becomes pronounced at later stages. 3. CT could be one of the most useful clinical tests available for the diagnosis of Alzheimer's disease. (orig.) [de

  14. A multimodal RAGE-specific inhibitor reduces amyloid β–mediated brain disorder in a mouse model of Alzheimer disease

    Science.gov (United States)

    Deane, Rashid; Singh, Itender; Sagare, Abhay P.; Bell, Robert D.; Ross, Nathan T.; LaRue, Barbra; Love, Rachal; Perry, Sheldon; Paquette, Nicole; Deane, Richard J.; Thiyagarajan, Meenakshisundaram; Zarcone, Troy; Fritz, Gunter; Friedman, Alan E.; Miller, Benjamin L.; Zlokovic, Berislav V.

    2012-01-01

    In Alzheimer disease (AD), amyloid β peptide (Aβ) accumulates in plaques in the brain. Receptor for advanced glycation end products (RAGE) mediates Aβ-induced perturbations in cerebral vessels, neurons, and microglia in AD. Here, we identified a high-affinity RAGE-specific inhibitor (FPS-ZM1) that blocked Aβ binding to the V domain of RAGE and inhibited Aβ40- and Aβ42-induced cellular stress in RAGE-expressing cells in vitro and in the mouse brain in vivo. FPS-ZM1 was nontoxic to mice and readily crossed the blood-brain barrier (BBB). In aged APPsw/0 mice overexpressing human Aβ-precursor protein, a transgenic mouse model of AD with established Aβ pathology, FPS-ZM1 inhibited RAGE-mediated influx of circulating Aβ40 and Aβ42 into the brain. In brain, FPS-ZM1 bound exclusively to RAGE, which inhibited β-secretase activity and Aβ production and suppressed microglia activation and the neuroinflammatory response. Blockade of RAGE actions at the BBB and in the brain reduced Aβ40 and Aβ42 levels in brain markedly and normalized cognitive performance and cerebral blood flow responses in aged APPsw/0 mice. Our data suggest that FPS-ZM1 is a potent multimodal RAGE blocker that effectively controls progression of Aβ-mediated brain disorder and that it may have the potential to be a disease-modifying agent for AD. PMID:22406537

  15. [Aβ immunotherapy for Alzheimer's disease].

    Science.gov (United States)

    Sakai, Kenji; Yamada, Masahito

    2013-04-01

    Alzheimer's disease (AD) is one of the neurodegenerative diseases characterized by the deposition of amyloid-β-protein (Aβ) as senile plaques in the brain parenchyma and phosphorylated-tau accumulation as neurofibrillary tangles in the neurons. Although details of the disease pathomechanisms remain unclear, Aβ likely acts as a key protein for AD initiation and progression, followed by abnormal tau phosphorylation and neuronal death (amyloid-cascade hypothesis). According to this hypothesis, Aβ immunization therapies are created to eliminate Aβ from the brain, and to prevent the neurons from damage by these pathogenic proteins. There are two methods for Aβ immunotherapies: active and passive immunization. Previous studies have shown Aβ removal and improved cognitive function in animal models of AD. Clinical trials on various drugs, including AN1792, bapineuzumab, and solanezumab, have been carried out; however, all trials have failed to demonstrate apparent clinical benefits. On the contrary, side effects emerged, such as meningoencephalitis, vasogenic edema, which are currently called amyloid related imaging abnormalities (ARIA)-E and microhemorrhage (ARIA-H). In neuropathological studies of immunized cases, Aβ was removed from the brain parenchyma and phosphorylated-tau was reduced in the neuronal processes. Moreover, deterioration of the cerebral amyloid angiopathy (CAA) and an increase of microhemorrhages and microinfarcts were described. Aβ is cleared from the brain mainly via the lymphatic drainage pathway. ARIA could stem from severe CAA due to dysfunction of the drainage pathway after immunotherapy. Aβ immunization has a potential of cure for AD patients, although the above-described problems must be overcome before applying this therapy in clinical treatment.

  16. In Alzheimer's disease, 6-month treatment with GLP-1 analog prevents decline of brain glucose metabolism

    DEFF Research Database (Denmark)

    Gejl, Michael; Gjedde, Albert; Egefjord, Lærke

    2016-01-01

    with AD to treatment with the GLP-1 analog liraglutide (n = 18), or placebo (n = 20). We measured Aβ load in brain with tracer [11C]PIB (PIB), CMRglc with [18F]FDG (FDG), and cognition with the WMS-IV scale (ClinicalTrials.gov NCT01469351). The PIB binding increased significantly in temporal lobe...... in placebo and treatment patients (both P = 0.04), and in occipital lobe in treatment patients (P = 0.04). Regional and global increases of PIB retention did not differ between the groups (P ≥ 0.38). In placebo treated patients CMRglc declined in all regions, significantly so by the following means...

  17. Alzheimer disease and anesthesia.

    Science.gov (United States)

    Inan, Gözde; Özköse Satirlar, Zerrin

    2015-01-01

    Alzheimer disease (AD) is one of the most common neurodegenerative diseases and the most prevalent form of dementia. Some factors in the development of AD, age being the best-known one, have been suggested; however, no causes have been found yet. The pathophysiology of the disease is highly complex, current therapies are palliative, and a cure is still lacking. Adverse effects of anesthetics in the elderly have been reported since the 1950s; however, awareness of this old problem has recently gained inportance again. Whether exposure to surgery and general anesthesia (GA) is associated with the development of AD has been questioned. As the population is aging, many elderly patients will need to be anesthetized, and maybe some were already anesthetized before they were diagnosed. Exposure to anesthetics has been demonstrated to promote pathogenesis of AD in both in vitro and in vivo studies. However, to date, there have not been any clinical trials to address a link between exposure to GA and the development of AD in humans. Therefore, before making any conclusions we need further studies, but we should be aware of the potential risks and take cautions with vulnerable elderly patients.

  18. Aluminum and Alzheimer's Disease.

    Science.gov (United States)

    Colomina, Maria Teresa; Peris-Sampedro, Fiona

    2017-01-01

    Aluminum (Al) is one of the most extended metals in the Earth's crust. Its abundance, together with the widespread use by humans, makes Al-related toxicity particularly relevant for human health.Despite some factors influence individual bioavailability to this metal after oral, dermal, or inhalation exposures, humans are considered to be protected against Al toxicity because of its low absorption and efficient renal excretion. However, several factors can modify Al absorption and distribution through the body, which may in turn progressively contribute to the development of silent chronic exposures that may lately trigger undesirable consequences to health. For instance, Al has been recurrently shown to cause encephalopathy, anemia, and bone disease in dialyzed patients. On the other hand, it remains controversial whether low doses of this metal may contribute to developing Alzheimer's disease (AD), probably because of the multifactorial and highly variable presentation of the disease.This chapter primarily focuses on two key aspects related to Al neurotoxicity and AD, which are metabolic impairment and iron (Fe) alterations. We discuss sex and genetic differences as a plausible source of bias to assess risk assessment in human populations.

  19. Cognitive reserve in ageing and Alzheimer's disease

    Science.gov (United States)

    Stern, Yaakov

    2012-01-01

    The concept of reserve accounts for individual differences in susceptibility to age-related brain changes or Alzheimer's disease-related pathology. There is evidence that some people can tolerate more of these changes than others and still maintain function. Epidemiologic studies suggest that lifetime exposures including educational and occupational attainment, and leisure activities in late life, can increase this reserve. For example, there is a reduced risk of developing Alzheimer's disease in individuals with higher educational or occupational attainment. It is convenient to think of two types of reserve: brain reserve, which refers to actual differences in the brain itself that may increase tolerance of pathology, and cognitive reserve. Cognitive reserve refers to individual differences in how tasks are performed that may allow some people to be more resilient than others. The concept of cognitive reserve holds out the promise of interventions that could slow cognitive aging or reduce the risk of dementia. PMID:23079557

  20. Application of PET in Alzheimer's disease

    International Nuclear Information System (INIS)

    Zhang Chun

    2003-01-01

    Alzheimer's disease (AD) is a neurodegenerative disease of central nervous system that causes progressive cognitive and memory deterioration in the elderly people. Affected brains of AD patients are characterized by the presence of senile plaques (SP) and neurofilbrillary tangles (NFT). The review will focus on the application of positron emission tomography (PET) in the diagnosis, progression prediction, treatment and evaluation of neurotransmission activity of AD

  1. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... Facts and Figures report contains data on the impact of this disease in every state across the nation. Click below to see the effect that Alzheimer's is having in your state. Read ...

  2. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... every 33 seconds. GET INVOLVED. Join the cause Mortality Alzheimer's disease is the only top 10 cause ... This dramatic rise includes more than four-fold increases both in government spending under Medicare and Medicaid ...

  3. Diagnosis and treatment of Alzheimer's disease

    International Nuclear Information System (INIS)

    Hampel, H.; Padberg, F.; Koetter, H.U.; Teipel, S.J.; Ehrhardt, T.; Hegerl, U.; Stuebner, S.; Moeller, H.J.

    1997-01-01

    Alzheimer's disease is often diagnosed too late. Its etiology is still largely unknown and remains one of the big challenges in neurobiological fundamental research. Optimized early and differential diagnosis can be ensured by a dynamic concept of multidisciplinary diagnosis in cooperation between practitioners specializing in brain disorders, clinical psychogeriatric deprtments, and general practitioners. This, in turn, will enable individualized planning of further living conditions and care of Alzheimer patients and their relations as well as efficient and early pharmacotherapy and psychological intervention. (orig) [de

  4. How Alzheimer's Changes the Brain

    Medline Plus

    Full Text Available ... Bredesen, MD - Duration: 1:13:27. Silicon Valley Health Institute 89,153 views 1:13:27 Mid ... Disease - Duration: 42:07. All N One Home Health 99,404 views 42:07 Your Amazing Brain - ...

  5. Quiz: Alzheimer's Disease Quiz | Alzheimer's disease | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: Alzheimer's Disease Quiz: Alzheimer's Disease Quiz Past Issues / Fall 2010 Table of ... How many people in the United States have Alzheimer's disease? as many as 5.1 million as ...

  6. [Late-onset Neurodegenerative Diseases Following Traumatic Brain Injury: Chronic Traumatic Encephalopathy (CTE) and Alzheimer's Disease Secondary to TBI (AD-TBI)].

    Science.gov (United States)

    Takahata, Keisuke; Tabuchi, Hajime; Mimura, Masaru

    2016-07-01

    Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease, which is associated with mild repetitive traumatic brain injury (TBI). This long-term and progressive symptom due to TBI was initially called punch-drunk syndrome or dementia pugilistica, since it was believed to be associated with boxing. However, serial neuropathological studies of mild repetitive TBI in the last decade have revealed that CTE occurs not only in boxers but also in a wider population including American football players, wrestlers, and military personnel. CTE has gained large public interest owing to dramatic cases involving retired professional athletes wherein serious behavioral problems and tragic incidents were reported. Unlike mild repetitive TBI, a single episode of severe TBI can cause another type of late-onset neuropsychiatric disease including Alzheimer's disease (AD). Several epidemiological studies have shown that a single episode of severe TBI is one of the major risk factors of AD. Pathologically, both AD and CTE are characterized by abnormal accumulations of hyperphosphorylated tau proteins. However, recent neuropathological studies revealed that CTE demonstrates a unique pattern of tau pathology in neurons and astrocytes, and accumulation of other misfolded proteins such as TDP-43. Currently, no reliable biomarkers of late-onset neurodegenerative diseases following TBI are available, and a definitive diagnosis can be made only via postmortem neuropathological examination. Development in neuroimaging techniques such as tau and amyloid positron emission tomography imaging might not only enable early diagnosis of CTE, but also contribute to the interventions for prevention of late-onset neurodegenerative diseases following TBI. Further studies are necessary to elucidate the mechanisms of neurodegeneration in the living brain of patients with TBI.

  7. Brain Imaging and Blood Biomarker Abnormalities in Children With Autosomal Dominant Alzheimer Disease: A Cross-Sectional Study.

    Science.gov (United States)

    Quiroz, Yakeel T; Schultz, Aaron P; Chen, Kewei; Protas, Hillary D; Brickhouse, Michael; Fleisher, Adam S; Langbaum, Jessica B; Thiyyagura, Pradeep; Fagan, Anne M; Shah, Aarti R; Muniz, Martha; Arboleda-Velasquez, Joseph F; Munoz, Claudia; Garcia, Gloria; Acosta-Baena, Natalia; Giraldo, Margarita; Tirado, Victoria; Ramírez, Dora L; Tariot, Pierre N; Dickerson, Bradford C; Sperling, Reisa A; Lopera, Francisco; Reiman, Eric M

    2015-08-01

    Brain imaging and fluid biomarkers are characterized in children at risk for autosomal dominant Alzheimer disease (ADAD). To characterize and compare structural magnetic resonance imaging (MRI), resting-state and task-dependent functional MRI, and plasma amyloid-β (Aβ) measurements in presenilin 1 (PSEN1) E280A mutation-carrying and noncarrying children with ADAD. Cross-sectional measures of structural and functional MRI and plasma Aβ assays were assessed in 18 PSEN1 E280A carriers and 19 noncarriers aged 9 to 17 years from a Colombian kindred with ADAD. Recruitment and data collection for this study were conducted at the University of Antioquia and the Hospital Pablo Tobon Uribe in Medellín, Colombia, between August 2011 and June 2012. All participants had blood sampling, structural MRI, and functional MRI during associative memory encoding and resting-state and cognitive assessments. Outcome measures included plasma Aβ1-42 concentrations and Aβ1-42:Aβ1-40 ratios, memory encoding-dependent activation changes, resting-state connectivity, and regional gray matter volumes. Structural and functional MRI data were compared using automated brain mapping algorithms and search regions related to AD. Similar to findings in adult mutation carriers, in the later preclinical and clinical stages of ADAD, mutation-carrying children were distinguished from control individuals by significantly higher plasma Aβ1-42 levels (mean [SD]: carriers, 18.8 [5.1] pg/mL and noncarriers, 13.1 [3.2] pg/mL; P < .001) and Aβ1-42:Aβ1-40 ratios (mean [SD]: carriers, 0.32 [0.06] and noncarriers, 0.21 [0.03]; P < .001), as well as less memory encoding task-related deactivation in parietal regions (eg, mean [SD] parameter estimates for the right precuneus were -0.590 [0.50] for noncarriers and -0.087 [0.38] for carriers; P < .005 uncorrected). Unlike carriers in the later stages, mutation-carrying children demonstrated increased functional connectivity of the posterior

  8. ImmunoPEGliposome-mediated reduction of blood and brain amyloid levels in a mouse model of Alzheimer's disease is restricted to aged animals

    DEFF Research Database (Denmark)

    Ordóñez-Gutiérrez, Lara; Posado-Fernández, Adrián; Ahmadvand, Davoud

    2017-01-01

    ) and THP-1 phagocytes (stimulating uptake) was confirmed in vitro. The multivalent immunoliposomes dramatically reduced circulating and brain levels of Aβ1-40, and particularly Aβ1-42, in "aged" (16 month-old), but not "adult" (10 month-old) APP/PS1 transgenic mice on repeated intraperitoneal......The accumulation of extracellular amyloid-beta (Aβ) and intracellular neurofibrillary tangles (hyper-phosphorylated Tau) in the brain are two major neuropathological hallmarks of Alzheimer's disease (AD). Active and passive immunotherapy may limit cerebral Aβ deposition and/or accelerate its...... clearance. With the aid of a newly characterized monoclonal anti-Aβ antibody we constructed immunoPEGliposomes with high avidity for capturing Aβ in the periphery. The functionality of these vesicles in modulating Aβ uptake by both human brain capillary endothelial hCMEC/D3 cells (suppressing uptake...

  9. A systematic integrated analysis of brain expression profiles reveals YAP1 and other prioritized hub genes as important upstream regulators in Alzheimer's disease.

    Science.gov (United States)

    Xu, Min; Zhang, Deng-Feng; Luo, Rongcan; Wu, Yong; Zhou, Hejiang; Kong, Li-Li; Bi, Rui; Yao, Yong-Gang

    2018-02-01

    Profiling the spatial-temporal expression pattern and characterizing the regulatory networks of brain tissues are vital for understanding the pathophysiology of Alzheimer's disease (AD). We performed a systematic integrated analysis of expression profiles of AD-affected brain tissues (684 AD and 562 controls). A network-based convergent functional genomic approach was used to prioritize possible regulator genes during AD development, followed by functional characterization. We generated a complete list of differentially expressed genes and hub genes of the transcriptomic network in AD brain and constructed a Web server (www.alzdata.org) for public access. Seventeen hub genes active at the early stages, especially YAP1, were recognized as upstream regulators of the AD network. Cellular assays proved that early alteration of YAP1 could promote AD by influencing the whole transcriptional network. Early expression disturbance of hub genes is an important feature of AD development, and interfering with this process may reverse the disease progression. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  10. Alzheimer's disease and intelligence.

    Science.gov (United States)

    Yeo, R A; Arden, R; Jung, R E

    2011-06-01

    A significant body of evidence has accumulated suggesting that individual variation in intellectual ability, whether assessed directly by intelligence tests or indirectly through proxy measures, is related to risk of developing Alzheimer's disease (AD) in later life. Important questions remain unanswered, however, such as the specificity of risk for AD vs. other forms of dementia, and the specific links between premorbid intelligence and development of the neuropathology characteristic of AD. Lower premorbid intelligence has also emerged as a risk factor for greater mortality across myriad health and mental health diagnoses. Genetic covariance contributes importantly to these associations, and pleiotropic genetic effects may impact diverse organ systems through similar processes, including inefficient design and oxidative stress. Through such processes, the genetic underpinnings of intelligence, specifically, mutation load, may also increase the risk of developing AD. We discuss how specific neurobiologic features of relatively lower premorbid intelligence, including reduced metabolic efficiency, may facilitate the development of AD neuropathology. The cognitive reserve hypothesis, the most widely accepted account of the intelligence-AD association, is reviewed in the context of this larger literature.

  11. The biological substrates of Alzheimer's disease

    International Nuclear Information System (INIS)

    Scheibel, A.B.; Wechsler, A.F.; Brazier, M.A.B.

    1986-01-01

    This book contains 21 selections. Some of the titles are: Dementia of the Alzheimer Type: Genetic Aspects; Determination of Cerebral Metabolic Patterns in Dementia Using Positron Emission Tomography; Pathology of the Basal Forebrain in Alzheimer's Disease and Other Dementias; Characterization of Neurofibrillary Tangles with Monoclonal Antibodies Raised Against Alzheimer Neurofibrillary Tangles; and HLA Associations in Alzheimer's Disease

  12. Anosognosia in Alzheimer's disease: A neuropsychological approach

    OpenAIRE

    Zilli, Bárbara Bomfim Caiado de Castro; Damasceno, Benito Pereira

    2007-01-01

    Abstract Anosognosia is often found in Alzheimer´s disease (AD), but its relationship with cognitivebehavioral changes is not well established. Objective: To verify if anosognosia is related to cognitive-behavioral disturbances, and to regional brain dysfunction as evaluated by neuroimaging. Methods: We included AD patients with Mini-Mental State Examination (MMSE) scores of 12 through 24, and Clinical Dementia Rating (CDR) scores of 1 or 2. Dementia diagnosis was based on DSM-IV and NINCDS...

  13. Alzheimer's disease and the fornix.

    Science.gov (United States)

    Oishi, Kenichi; Lyketsos, Constantine G

    2014-01-01

    Alzheimer's disease (AD) is the most common form of neurodegenerative dementia. Researchers have long been focused on the cortical pathology of AD, since the most important pathologic features are the senile plaques found in the cortex, and the neurofibrillary tangles and neuronal loss that begin in the entorhinal cortex and the hippocampus. In addition to these gray matter (GM) structures, histopathological studies indicate that the white matter (WM) is also a good target for both the early diagnosis of AD and for monitoring disease progression. The fornix is a WM bundle that constitutes a core element of the limbic circuits, and is one of the most important anatomical structures related to memory. Functional and anatomical features of the fornix have naturally captured researchers' attention as possible diagnostic and prognostic markers of AD. Indeed, neurodegeneration of the fornix has been histologically observed in AD, and growing evidence indicates that the alterations seen in the fornix are potentially a good marker to predict future conversion from mild cognitive impairment (MCI) to AD, and even from cognitively normal individuals to AD. The degree of alteration is correlated with the degree of memory impairment, indicating the potential for the use of the fornix as a functional marker. Moreover, there have been attempts to stimulate the fornix using deep brain stimulation (DBS) to augment cognitive function in AD, and ongoing research has suggested positive effects of DBS on brain glucose metabolism in AD patients. On the other hand, disease specificity for fornix degeneration, methodologies to evaluate fornix degeneration, and the clinical significance of the fornix DBS, especially for the long-term impact on the quality of life, are mostly unknown and need to be elucidated.

  14. Brain in situ hybridization maps as a source for reverse-engineering transcriptional regulatory networks: Alzheimer's disease insights

    Energy Technology Data Exchange (ETDEWEB)

    Acquaah-Mensah, George K.; Taylor, Ronald C.

    2016-07-01

    Microarray data have been a valuable resource for identifying transcriptional regulatory relationships among genes. As an example, brain region-specific transcriptional regulatory events have the potential of providing etiological insights into Alzheimer Disease (AD). However, there is often a paucity of suitable brain-region specific expression data obtained via microarrays or other high throughput means. The Allen Brain Atlas in situ hybridization (ISH) data sets (Jones et al., 2009) represent a potentially valuable alternative source of high-throughput brain region-specific gene expression data for such purposes. In this study, Allen BrainAtlasmouse ISH data in the hippocampal fields were extracted, focusing on 508 genes relevant to neurodegeneration. Transcriptional regulatory networkswere learned using three high-performing network inference algorithms. Only 17% of regulatory edges from a network reverse-engineered based on brain region-specific ISH data were also found in a network constructed upon gene expression correlations inmousewhole brain microarrays, thus showing the specificity of gene expression within brain sub-regions. Furthermore, the ISH data-based networks were used to identify instructive transcriptional regulatory relationships. Ncor2, Sp3 and Usf2 form a unique three-party regulatory motif, potentially affecting memory formation pathways. Nfe2l1, Egr1 and Usf2 emerge among regulators of genes involved in AD (e.g. Dhcr24, Aplp2, Tia1, Pdrx1, Vdac1, andSyn2). Further, Nfe2l1, Egr1 and Usf2 are sensitive to dietary factors and could be among links between dietary influences and genes in the AD etiology. Thus, this approach of harnessing brain region-specific ISH data represents a rare opportunity for gleaning unique etiological insights for diseases such as AD.

  15. Nutritional supplementation for Alzheimer's disease?

    Science.gov (United States)

    Shea, Thomas B; Remington, Ruth

    2015-03-01

    Evidence for the benefit of nutrition in Alzheimer's disease continues to accumulate. Many studies with individual vitamins or supplements show marginal, if any, benefit. However, new findings with combinatorial formulations demonstrate improvement in cognitive performance and behavioral difficulties that accompany Alzheimer's disease. Herein, we review some of the most recent clinical advances and summarize supportive preclinical studies. We present novel positive effects on Alzheimer's disease derived from diet, trace elements, vitamins and supplements. We discuss the inherent difficulty in conducting nutritional studies because of the variance in participants' nutritional history, versus pharmacological interventions in which participants are naive to the intervention. We examine the evidence that epigenetics play a role in Alzheimer's disease and how nutritional intervention can modify the key epigenetic events to maintain or improve cognitive performance. Overall consideration of the most recent collective evidence suggests that the optimal approach for Alzheimer's disease would seem to combine early, multicomponent nutritional approaches (a Mediterranean-style diet, multivitamins and key combinatorial supplements), along with lifestyle modifications such as social activity and mental and physical exercise, with ultimate addition of pharmacological agents when warranted.

  16. Ayurvedic Profiling of Alzheimer's Disease.

    Science.gov (United States)

    Bredesen, Dale E; Rao, Rammohan V

    2017-05-01

    Alzheimer's disease (AD) is an age-associated, progressive neurodegenerative disease that is characterized by severe memory loss, personality changes, and an overall decline in cognitive function. The cause of AD is not yet completely defined and efforts to find a cure for it have so far been disappointing. AD is one of the most significant health care problems nationally and globally. Recently, we described a personalized therapeutic approach called metabolic enhancement for neurodegeneration (MEND) that successfully reversed the cognitive decline in patients with early AD. The magnitude of the improvement was exceptional, providing testimony to the fact that a personalized and programmatic approach to cognitive decline is highly effective. Ayurveda is a personalized system of traditional medicine native to India and the Indian subcontinent. Although a direct reference to AD in the ancient Ayurvedic literature is missing, concepts including forgetfulness, memory loss, and brain cell loss have been described. Using the clinical information and the metabolic profiling of AD individuals we recently reported using the MEND program, we now describe in this commentary, 3 subtypes of AD based on the Ayurvedic interpretation. Ayurvedic profiling of patients with AD reveals 3 readily distinguishable subtypes, namely Vata, Pitta, and Krimi, which will prove useful in patients with cognitive decline and those at risk for such decline from the standpoint of specific subtype-based Ayurvedic intervention.

  17. Alzheimer's Disease and the Eye

    Directory of Open Access Journals (Sweden)

    Richard A. Armstrong

    2009-01-01

    Full Text Available Dementia, including Alzheimer's disease (AD, is a major disorder causing visual problems in the elderly population. The pathology of AD includes the deposition in the brain of abnormal aggregates of β-amyloid (Aβ in the form of senile plaques (SP and abnormally phosphorylated tau in the form of neurofibrillary tangles (NFT. A variety of visual problems have been reported in patients with AD including loss of visual acuity (VA, colour vision and visual fields; changes in pupillary response to mydriatics, defects in fixation and in smooth and saccadic eye movements; changes in contrast sensitivity and in visual evoked potentials (VEP; and disturbances of complex visual functions such as reading, visuospatial function, and in the naming and identification of objects. Many of these changes are controversial with conflicting data in the literature and no ocular or visual feature can be regarded as particularly diagnostic of AD. In addition, some pathological changes have been observed to affect the eye, visual pathway, and visual cortex in AD. The optometrist has a role in helping a patient with AD, if it is believed that signs and symptoms of the disease are present, so as to optimize visual function and improve the quality of life.

  18. Alzheimer's Disease and the Eye☆

    Science.gov (United States)

    Armstrong, Richard A.

    2010-01-01

    Dementia, including Alzheimer's disease (AD), is a major disorder causing visual problems in the elderly population. The pathology of AD includes the deposition in the brain of abnormal aggregates of β-amyloid (Aβ) in the form of senile plaques (SP) and abnormally phosphorylated tau in the form of neurofibrillary tangles (NFT). A variety of visual problems have been reported in patients with AD including loss of visual acuity (VA), colour vision and visual fields; changes in pupillary response to mydriatics, defects in fixation and in smooth and saccadic eye movements; changes in contrast sensitivity and in visual evoked potentials (VEP); and disturbances of complex visual functions such as reading, visuospatial function, and in the naming and identification of objects. Many of these changes are controversial with conflicting data in the literature and no ocular or visual feature can be regarded as particularly diagnostic of AD. In addition, some pathological changes have been observed to affect the eye, visual pathway, and visual cortex in AD. The optometrist has a role in helping a patient with AD, if it is believed that signs and symptoms of the disease are present, so as to optimize visual function and improve the quality of life.

  19. A Food and Drug Administration-approved asthma therapeutic agent impacts amyloid β in the brain in a transgenic model of Alzheimer disease.

    Science.gov (United States)

    Hori, Yukiko; Takeda, Shuko; Cho, Hansang; Wegmann, Susanne; Shoup, Timothy M; Takahashi, Kazue; Irimia, Daniel; Elmaleh, David R; Hyman, Bradley T; Hudry, Eloise

    2015-01-23

    Interfering with the assembly of Amyloid β (Aβ) peptides from monomer to oligomeric species and fibrils or promoting their clearance from the brain are targets of anti-Aβ-directed therapies in Alzheimer disease. Here we demonstrate that cromolyn sodium (disodium cromoglycate), a Food and Drug Administration-approved drug already in use for the treatment of asthma, efficiently inhibits the aggregation of Aβ monomers into higher-order oligomers and fibrils in vitro without affecting Aβ production. In vivo, the levels of soluble Aβ are decreased by over 50% after only 1 week of daily intraperitoneally administered cromolyn sodium. Additional in vivo microdialysis studies also show that this compound decreases the half-life of soluble Aβ in the brain. These data suggest a clear effect of a peripherally administered, Food and Drug Administration-approved medication on Aβ economy, supporting further investigation of the potential long-term efficacy of cromolyn sodium in Alzheimer disease. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Traffic jam at the blood-brain barrier promotes greater accumulation of Alzheimer's disease amyloid-β proteins in the cerebral vasculature.

    Science.gov (United States)

    Agyare, Edward K; Leonard, Sarah R; Curran, Geoffry L; Yu, Caroline C; Lowe, Val J; Paravastu, Anant K; Poduslo, Joseph F; Kandimalla, Karunya K

    2013-05-06

    Amyloid-β (Aβ) deposition in the brain vasculature results in cerebral amyloid angiopathy (CAA), which occurs in about 80% of Alzheimer's disease (AD) patients. While Aβ42 predominates parenchymal amyloid plaques in AD brain, Aβ40 is prevalent in the cerebrovascular amyloid. Dutch mutation of Aβ40 (E22Q) promotes aggressive cerebrovascular accumulation and leads to severe CAA in the mutation carriers; knowledge of how DutchAβ40 drives this process more efficiently than Aβ40 could reveal various pathophysiological events that promote CAA. In this study we have demonstrated that DutchAβ40 shows preferential accumulation in the blood-brain-barrier (BBB) endothelial cells due to its inefficient blood-to-brain transcytosis. Consequently, DutchAβ40 establishes a permeation barrier in the BBB endothelium, prevents its own clearance from the brain, and promotes the formation of amyloid deposits in the cerebral microvessels. The BBB endothelial accumulation of native Aβ40 is not robust enough to exercise such a significant impact on its brain clearance. Hence, the cerebrovascular accumulation of Aβ40 is slow and may require other copathologies to precipitate into CAA. In conclusion, the magnitude of Aβ accumulation in the BBB endothelial cells is a critical factor that promotes CAA; hence, clearing vascular endothelium of Aβ proteins may halt or even reverse CAA.

  1. Radiopharmaceuticals for Assessment of Altered Metabolism and Biometal Fluxes in Brain Aging and Alzheimer's Disease with Positron Emission Tomography.

    Science.gov (United States)

    Xie, Fang; Peng, Fangyu

    2017-01-01

    Aging is a risk factor for Alzheimer's disease (AD). There are changes of brain metabolism and biometal fluxes due to brain aging, which may play a role in pathogenesis of AD. Positron emission tomography (PET) is a versatile tool for tracking alteration of metabolism and biometal fluxes due to brain aging and AD. Age-dependent changes in cerebral glucose metabolism can be tracked with PET using 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG), a radiolabeled glucose analogue, as a radiotracer. Based on different patterns of altered cerebral glucose metabolism, 18F-FDG PET was clinically used for differential diagnosis of AD and Frontotemporal dementia (FTD). There are continued efforts to develop additional radiopharmaceuticals or radiotracers for assessment of age-dependent changes of various metabolic pathways and biometal fluxes due to brain aging and AD with PET. Elucidation of age-dependent changes of brain metabolism and altered biometal fluxes is not only significant for a better mechanistic understanding of brain aging and the pathophysiology of AD, but also significant for identification of new targets for the prevention, early diagnosis, and treatment of AD.

  2. Ophthalmic examination in early diagnosis of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Xin Li

    2018-02-01

    Full Text Available Alzheimer's disease is a progressive neurodegenerative disorder causing irreversible deterioration in memory and loss of self-care ability, which is seriously affecting the quality of life. There is no cure for Alzheimer's disease. Medication only can control the progression of the disease. Early diagnosis and control of disease progress is of great significance in improving the quality of life of the patients and reducing the burden of family and society. Ophthalmic examination is seen as a window which can “see” brain directly, and some changes in the eye can reflect the changes of the brain most directly. This paper reviews the ophthalmic examination of Alzheimer's disease, including optical coherence tomography(OCT, visual field, contrast sensitivity and eye movements, et al. We hope to provide a new idea for the early diagnosis of Alzheimer's disease.

  3. Insulin and Alzheimer disease: type 3 diabetes?

    Directory of Open Access Journals (Sweden)

    Andrés Jagua Gualdrón

    2007-01-01

    Full Text Available Alzheimer Disease is a neurodegenerative disease of central nervous system whose incidence will increase in next years. Recent investigations relate alzheimer with insulin signaling defects in neurons. Is alzheimer Disease a type 3 diabetes? In this communication write a brief article about evidences from this alzheimer‘s disease model.

  4. Improved Mitochondrial Function in Brain Aging and Alzheimer Disease – the New Mechanism of Action of the Old Metabolic Enhancer Piracetam

    Science.gov (United States)

    Leuner, Kristina; Kurz, Christopher; Guidetti, Giorgio; Orgogozo, Jean-Marc; Müller, Walter E.

    2010-01-01

    Piracetam, the prototype of the so-called nootropic drugs’ is used since many years in different countries to treat cognitive impairment in aging and dementia. Findings that piracetam enhances fluidity of brain mitochondrial membranes led to the hypothesis that piracetam might improve mitochondrial function, e.g., might enhance ATP synthesis. This assumption has recently been supported by a number of observations showing enhanced mitochondrial membrane potential, enhanced ATP production, and reduced sensitivity for apoptosis in a variety of cell and animal models for aging and Alzheimer disease. As a specific consequence, substantial evidence for elevated neuronal plasticity as a specific effect of piracetam has emerged. Taken together, this new findings can explain many of the therapeutic effects of piracetam on cognition in aging and dementia as well as different situations of brain dysfunctions. PMID:20877425

  5. Context memory in Alzheimer's disease

    NARCIS (Netherlands)

    El Haj, M.; Kessels, R.P.C.

    2013-01-01

    Background: Alzheimer's disease (AD) is a neurodegenerative disease characterized by a gradual loss of memory. Specifically, context aspects of memory are impaired in AD. Our review sheds light on the neurocognitive mechanisms of this memory component that forms the core of episodic memory function.

  6. Alzheimer's Disease. LC Science Tracer Bullet 87-2.

    Science.gov (United States)

    Sammons, Vivian O., Comp.

    Alzheimer's disease is characterized by a degeneration and shrinkage of brain tissue; the symptoms include progressive memory loss, bizarre behavior, difficulty in speaking and walking, incontinence, and confusion. Positive diagnosis is possible only upon examination of brain tissue at autopsy. The disease affects not only the patient but also the…

  7. Optimizing power to track brain degeneration in Alzheimer's disease and mild cognitive impairment with tensor-based morphometry: an ADNI study of 515 subjects.

    Science.gov (United States)

    Hua, Xue; Lee, Suh; Yanovsky, Igor; Leow, Alex D; Chou, Yi-Yu; Ho, April J; Gutman, Boris; Toga, Arthur W; Jack, Clifford R; Bernstein, Matt A; Reiman, Eric M; Harvey, Danielle J; Kornak, John; Schuff, Norbert; Alexander, Gene E; Weiner, Michael W; Thompson, Paul M

    2009-12-01

    Tensor-based morphometry (TBM) is a powerful method to map the 3D profile of brain degeneration in Alzheimer's disease (AD) and mild cognitive impairment (MCI). We optimized a TBM-based image analysis method to determine what methodological factors, and which image-derived measures, maximize statistical power to track brain change. 3D maps, tracking rates of structural atrophy over time, were created from 1030 longitudinal brain MRI scans (1-year follow-up) of 104 AD patients (age: 75.7+/-7.2 years; MMSE: 23.3+/-1.8, at baseline), 254 amnestic MCI subjects (75.0+/-7.2 years; 27.0+/-1.8), and 157 healthy elderly subjects (75.9+/-5.1 years; 29.1+/-1.0), as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI). To determine which TBM designs gave greatest statistical power, we compared different linear and nonlinear registration parameters (including different regularization functions), and different numerical summary measures derived from the maps. Detection power was greatly enhanced by summarizing changes in a statistically-defined region-of-interest (ROI) derived from an independent training sample of 22 AD patients. Effect sizes were compared using cumulative distribution function (CDF) plots and false discovery rate methods. In power analyses, the best method required only 48 AD and 88 MCI subjects to give 80% power to detect a 25% reduction in the mean annual change using a two-sided test (at alpha=0.05). This is a drastic sample size reduction relative to using clinical scores as outcome measures (619 AD/6797 MCI for the ADAS-Cog, and 408 AD/796 MCI for the Clinical Dementia Rating sum-of-boxes scores). TBM offers high statistical power to track brain changes in large, multi-site neuroimaging studies and clinical trials of AD.

  8. Neuroprotective effect of the active components of three Chinese herbs on brain iron load in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Dong, Xian-Hui; Gao, Wei-Juan; Kong, Wei-Na; Xie, Hong-Lin; Peng, Yan; Shao, Tie-Mei; Yu, Wen-Guo; Chai, Xi-Qing

    2015-04-01

    Alzheimer's disease (AD) is a neurodegenerative brain disorder and the most common cause of dementia. New treatments for AD are required due to its increasing prevalence in aging populations. The present study evaluated the effects of the active components of Epimedium , Astragalus and Radix Puerariae on learning and memory impairment, β-amyloid (Aβ) reduction and brain iron load in an APP swe /PS1 ΔE9 transgenic mouse model of AD. Increasing evidence indicates that a disturbance of normal iron homeostasis may contribute to the pathology of AD. However, the underlying mechanisms resulting in abnormal iron load in the AD brain remain unclear. It has been hypothesized that the brain iron load is influenced by the deregulation of certain proteins associated with brain iron metabolism, including divalent metal transporter 1 (DMT1) and ferroportin 1 (FPN1). The present study investigated the effects of the active components of Epimedium , Astragalus and Radix Puerariae on the expression levels of DMT1 and FPN1. The treatment with the active components reduced cognitive deficits, inhibited Aβ plaque accumulation, reversed Aβ burden and reduced the brain iron load in AD model mice. A significant increase was observed in the levels of DMT1-iron-responsive element (IRE) and DMT1-nonIRE in the hippocampus of the AD mouse brain, which was reduced by treatment with the active components. In addition, the levels of FPN1 were significantly reduced in the hippocampus of the AD mouse brain compared with those of control mice, and these levels were increased following treatment with the active components. Thus, the present study indicated that the active components of Epimedium , Astragalus and Radix Puerariae may exert a neuroprotective effect against AD by reducing iron overload in the AD brain and may provide a novel approach for the development of drugs for the treatment of AD.

  9. Reduction of Alzheimer's disease beta-amyloid pathology in the absence of gut microbiota

    OpenAIRE

    Harach, T.; Marungruang, N.; Dutilleul, N.; Cheatham, V.; Coy, K. D. Mc; Neher, J. J.; Jucker, M.; Fåk, F.; T.; Lasser; Bolmont, T.

    2015-01-01

    Alzheimer's disease is the most common form of dementia in the western world, however there is no cure available for this devastating neurodegenerative disorder. Despite clinical and experimental evidence implicating the intestinal microbiota in a number of brain disorders, its impact on Alzheimer's disease is not known. We generated a germ-free mouse model of Alzheimer's disease and discovered a drastic reduction of cerebral Ab amyloid pathology when compared to control Alzheimer's disease a...

  10. Exploring Symmetry to Assist Alzheimer's Disease Diagnosis

    Science.gov (United States)

    Illán, I. A.; Górriz, J. M.; Ramírez, J.; Salas-Gonzalez, D.; López, M.; Padilla, P.; Chaves, R.; Segovia, F.; Puntonet, C. G.

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder first affecting memory functions and then gradually affecting all cognitive functions with behavioral impairments and eventually causing death. Functional brain imaging as Single-Photon Emission Computed Tomography (SPECT) is commonly used to guide the clinician's diagnosis. The essential left-right symmetry of human brains is shown to play a key role in coding and recognition. In the present work we explore the implications of this symmetry in AD diagnosis, showing that recognition may be enhanced when considering this latent symmetry.

  11. microRNA in Cerebral Spinal Fluid as Biomarkers of Alzheimer’s Disease Risk After Brain Injury

    Science.gov (United States)

    2017-08-01

    AWARD NUMBER: W81XWH-15-1-0318 TITLE: microRNA in Cerebral Spinal Fluid as Biomarkers of Alzheimer’s Disease Risk After Brain Injury...After Brain Injury 5b. GRANT NUMBER AZ14046 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) J 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER...responses to brain injury that precede, and likely drive, changes in protein expression that lead to the development of AD. We have additional preliminary

  12. REVIEW: Curcumin and Alzheimer's disease.

    Science.gov (United States)

    Hamaguchi, Tsuyoshi; Ono, Kenjiro; Yamada, Masahito

    2010-10-01

    Curcumin has a long history of use as a traditional remedy and food in Asia. Many studies have reported that curcumin has various beneficial properties, such as antioxidant, antiinflammatory, and antitumor. Because of the reported effects of curcumin on tumors, many clinical trials have been performed to elucidate curcumin's effects on cancers. Recent reports have suggested therapeutic potential of curcumin in the pathophysiology of Alzheimer's disease (AD). In in vitro studies, curcumin has been reported to inhibit amyloid-β-protein (Aβ) aggregation, and Aβ-induced inflammation, as well as the activities of β-secretase and acetylcholinesterase. In in vivo studies, oral administration of curcumin has resulted in the inhibition of Aβ deposition, Aβ oligomerization, and tau phosphorylation in the brains of AD animal models, and improvements in behavioral impairment in animal models. These findings suggest that curcumin might be one of the most promising compounds for the development of AD therapies. At present, four clinical trials concerning the effects of curcumin on AD has been conducted. Two of them that were performed in China and USA have been reported no significant differences in changes in cognitive function between placebo and curcumin groups, and no results have been reported from two other clinical studies. Additional trials are necessary to determine the clinical usefulness of curcumin in the prevention and treatment of AD. © 2010 Blackwell Publishing Ltd.

  13. Angiotensin II, hypertension and angiotensin II receptor antagonism: Roles in the behavioural and brain pathology of a mouse model of Alzheimer's disease

    NARCIS (Netherlands)

    Wiesmann, M.; Roelofs, M.; Lugt, R. Van Der; Heerschap, A.; Kiliaan, A.J.; Claassen, J.A.H.R.

    2017-01-01

    Elevated angiotensin II causes hypertension and contributes to Alzheimer's disease by affecting cerebral blood flow. Angiotensin II receptor blockers may provide candidates to reduce (vascular) risk factors for Alzheimer's disease. We studied effects of two months of angiotensin II-induced

  14. Brain catalase in the streptozotocin-rat model of sporadic Alzheimer's disease treated with the iron chelator-monoamine oxidase inhibitor, M30.

    Science.gov (United States)

    Sofic, E; Salkovic-Petrisic, M; Tahirovic, I; Sapcanin, A; Mandel, S; Youdim, M; Riederer, P

    2015-04-01

    Low intracerebroventricular (icv) doses of streptozotocin (STZ) produce regionally specific brain neurochemical changes in rats that are similar to those found in the brain of patients with sporadic Alzheimer's disease (sAD). Since oxidative stress is thought to be one of the major pathologic processes in sAD, catalase (CAT) activity was estimated in the regional brain tissue of animals treated intracerebroventricularly with STZ and the multitarget iron chelator, antioxidant and MAO-inhibitor M30 [5-(N-methyl-N-propargylaminomethyl)-8-hydroxyquinoline]. Five-day oral pre-treatment of adult male Wistar rats with 10 mg/kg/day M30 dose was followed by a single injection of STZ (1 mg/kg, icv). CAT activity was measured colorimetrically in the hippocampus (HPC), brain stem (BS) and cerebellum (CB) of the control, STZ-, M30- and STZ + M30-treated rats, respectively, 4 weeks after the STZ treatment. STZ-treated rats demonstrated significantly lower CAT activity in all three brain regions in comparison to the controls (p effects in this non-transgenic sAD model.

  15. Alzheimer's Disease Brain-Derived Amyloid-{beta}-Mediated Inhibition of LTP In Vivo Is Prevented by Immunotargeting Cellular Prion Protein.

    LENUS (Irish Health Repository)

    Barry, Andrew E

    2011-05-18

    Synthetic amyloid-β protein (Aβ) oligomers bind with high affinity to cellular prion protein (PrP(C)), but the role of this interaction in mediating the disruption of synaptic plasticity by such soluble Aβ in vitro is controversial. Here we report that intracerebroventricular injection of Aβ-containing aqueous extracts of Alzheimer\\'s disease (AD) brain robustly inhibits long-term potentiation (LTP) without significantly affecting baseline excitatory synaptic transmission in the rat hippocampus in vivo. Moreover, the disruption of LTP was abrogated by immunodepletion of Aβ. Importantly, intracerebroventricular administration of antigen-binding antibody fragment D13, directed to a putative Aβ-binding site on PrP(C), prevented the inhibition of LTP by AD brain-derived Aβ. In contrast, R1, a Fab directed to the C terminus of PrP(C), a region not implicated in binding of Aβ, did not significantly affect the Aβ-mediated inhibition of LTP. These data support the pathophysiological significance of SDS-stable Aβ dimer and the role of PrP(C) in mediating synaptic plasticity disruption by soluble Aβ.

  16. Early-onset Alzheimer's Disease Phenotypes: Neuropsychology and Neural Networks

    Science.gov (United States)

    2017-05-11

    Alzheimer Disease, Early Onset; Alzheimer Disease; Alzheimer Disease, Late Onset; Dementia, Alzheimer Type; Logopenic Progressive Aphasia; Primary Progressive Aphasia; Visuospatial/Perceptual Abilities; Posterior Cortical Atrophy; Executive Dysfunction; Corticobasal Degeneration; Ideomotor Apraxia

  17. Coping & Caring: Living with Alzheimer's Disease.

    Science.gov (United States)

    Leroux, Charles

    This guide on Alzheimer's disease is for those who care for Alzheimer's patients, as well as those who want to learn more about the disease. It answers these questions: (1) what is Alzheimer's? (2) how does the disease progress and how long does it last? (3) how do families cope? and (4) who can provide assistance and information? The guide also…

  18. Aberrant brain-stem morphometry associated with sleep disturbance in drug-naïve subjects with Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Lee JH

    2016-08-01

    Full Text Available Ji Han Lee,1 Won Sang Jung,2 Woo Hee Choi,3 Hyun Kook Lim4 1Washington University in St Louis, St Louis, MO, USA; 2Department of Radiology, 3Department of Nuclear Medicine, 4Department of Psychiatry, Saint Vincent Hospital, College of Medicine, The Catholic University of Korea, Suwon, South Korea Objective: Among patients with Alzheimer’s disease (AD, sleep disturbances are common and serious noncognitive symptoms. Previous studies of AD patients have identified deformations in the brain stem, which may play an important role in the regulation of sleep. The aim of this study was to further investigate the relationship between sleep disturbances and alterations in brain stem morphology in AD.Materials and methods: In 44 patients with AD and 40 healthy elderly controls, sleep disturbances were measured using the Neuropsychiatry Inventory sleep subscale. We employed magnetic resonance imaging-based automated segmentation tools to examine the relationship between sleep disturbances and changes in brain stem morphology.Results: Analyses of the data from AD subjects revealed significant correlations between the Neuropsychiatry Inventory sleep-subscale scores and structural alterations in the left posterior lateral region of the brain stem, as well as normalized brain stem volumes. In addition, significant group differences in posterior brain stem morphology were observed between the AD group and the control group.Conclusion: This study is the first to analyze an association between sleep disturbances and brain stem morphology in AD. In line with previous findings, this study lends support to the possibility that brain stem structural abnormalities might be important neurobiological mechanisms underlying sleep disturbances associated with AD. Further longitudinal research is needed to confirm these findings. Keywords: Alzheimer’s disease, sleep, brain stem, MRI, shape analysis

  19. How Alzheimer's Changes the Brain

    Medline Plus

    Full Text Available ... roof: Dale Bredesen - Duration: 9:29. Ford Brewer 1,815 views 9:29 Papa late stage Alzheimer's 9/28/14 - Duration: 3:39. Debbie Templeton 19,479 views 3:39 Type 3 Diabetes: The Connection between Alzheimer’s and Metabolic Syndrome - Duration: ...

  20. How Alzheimer's Changes the Brain

    Medline Plus

    Full Text Available ... Bredesen, MD - Duration: 1:13:27. Silicon Valley Health Institute 91,457 views 1:13:27 5 ... and Symptoms of Alzheimer's - Duration: 2:20. Your Health Journey 172,451 views 2:20 Mid to ...

  1. How Alzheimer's Changes the Brain

    Medline Plus

    Full Text Available ... 17. TEDx Talks 12,392 views 12:17 Alzheimer’s Is Not Normal Aging — And We Can Cure It | Samuel Cohen | TED Talks - Duration: 7:54. TED 286,506 views 7:54 Day in the Life of an Alzheimer's Caregiver: Heartbreaking - Duration: 4:39. DavidNazarNews 31,783 ...

  2. How Alzheimer's Changes the Brain

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    Full Text Available ... Blaylock M.D 121,120 views 33:27 Kids Meet a Woman with Alzheimer's | Cut - Duration: 5: ... Loading... Loading... About Press Copyright Creators Advertise Developers +YouTube Terms Privacy Policy & Safety Send feedback Test new ...

  3. How Alzheimer's Changes the Brain

    Medline Plus

    Full Text Available ... Bredesen, MD - Duration: 1:13:27. Silicon Valley Health Institute 91,988 views 1:13:27 Your ... and Symptoms of Alzheimer's - Duration: 2:20. Your Health Journey 172,694 views 2:20 Alzheimer’s Is ...

  4. How Alzheimer's Changes the Brain

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    Full Text Available ... On Aging? Cancel Unsubscribe Working... Subscribe Subscribed Unsubscribe 5.3K Loading... Loading... Working... Add to Want to ... Kids Meet a Woman with Alzheimer's | Cut - Duration: 5:15. Cut 6,803,846 views 5:15 ...

  5. Perception of Alzheimer Disease in Iranian Traditional Medicine.

    Science.gov (United States)

    Saifadini, Rostam; Tajadini, Haleh; Choopani, Rasool; Mehrabani, Mitra; Kamalinegad, Mohamad; Haghdoost, Aliakbar

    2016-03-01

    Alzheimer disease (AD) is the most common cause of dementia. In regards to the world's aging population, control and treatment of AD will be one of the major concerns of global public health in the next century. Alzheimer disease was not mentioned with the same phrase or its equivalent in traditional medical texts. The main of present paper was to investigate symptoms and causes of alzheimer disease from the view point of Iranian traditional medicine. In this qualitative study, we searched reliable sources of Iranian traditional medicine such as Canon of Medicide by Avicenna (Al-Quanon fi- tibb), Aghili cure by Aghili's (Molajat-E-aghili), Tib-E-Akbari, Exire -E-Aazam and Sharh-E-Asbab and some reliable resources of neurology were probed base on keywords to find a disease that had the most overlap in terms of symptoms with alzheimer disease. By taking from the relevant materials, the extracted texts were compared and analyzed. Findings showed that alzheimer disease has the most overlap with Nesyan (fisad-e-zekr, fisad-e-fekr and fisad-e-takhayol) symptoms in Iranian traditional medicine. Although this is not a perfect overlap and there are causes, including coldness and dryness of the brain or coldness and wetness that could also lead to alzheimer disease according to Iranian traditional medicine. According to Iranian traditional medicine, The brain dystemperement is considered the main causes of alzheimer disease. By correcting the brain dystemperement, alzheimer can be well managed. This study helps to suggest a better strategy for preventing and treating alzheimer in the future.

  6. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... An estimated 5.5 million Americans of all ages have Alzheimer's disease. Of the estimated 5.5 ... in 2017, an estimated 5.3 million are age 65 and older and approximately 200,000 individuals ...

  7. Caregiver Response to Alzheimer's Disease.

    Science.gov (United States)

    Novak, Mark; Guest, Carol

    1989-01-01

    Examined correlates of caregiver burden among 30 caregivers of Alzheimer's disease patients. Results revealed no significant correlation between length of time a caregiver had given care to a particular patient and the caregiver's subjective feelings of caregiver burden. Found significant, moderate correlation between caregiver burden and patient…

  8. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... get Alzheimer's disease were diagnosed in the mild cognitive impairment (MCI) stage — before dementia — it would collectively save $7 trillion to $7.9 trillion in health and long-term care costs. worried about memory ...

  9. Head trauma and Alzheimer's disease

    NARCIS (Netherlands)

    Nandoe, Rishi D. S.; Scheltens, Philip; Eikelenboom, Piet

    2002-01-01

    The authors describe a case of a 55 year old woman who was diagnosed with Alzheimer's disease 1.5 years after a car accident in which she experienced a mild concussion. Extensive history taking disclosed no cognitive changes prior to the car accident. The case is discussed in view of the

  10. Genome instability in Alzheimer disease

    DEFF Research Database (Denmark)

    Hou, Yujun; Song, Hyundong; Croteau, Deborah L

    2017-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia. Autosomal dominant, familial AD (fAD) is very rare and caused by mutations in amyloid precursor protein (APP), presenilin-1 (PSEN-1), and presenilin-2 (PSEN-2) genes. The pathogenesis...

  11. Pharmacologic management of Alzheimer disease.

    Science.gov (United States)

    Downey, Deborah

    2008-02-01

    Although the diagnosis of AD can be devastating, treatment options exist that can slow the disease's progression and allow patients to continue performing ADLs, thereby improving the quality of life for both patient and caregiver. Research is ongoing, and it is estimated by the Alzheimer's Association that finding a treatment that could delay onset by only 5 years could reduce the number of individuals with AD by nearly 50% over the next 50 years (Alzheimer's Association, 2007). Although pharmacotherapy is not yet a cure, it does remain an important part of a total approach to caring for patients and families affected by AD.

  12. Positron emission tomography measurement of brain MAO-B inhibition in patients with Alzheimer's disease and elderly controls after oral administration of sembragiline

    International Nuclear Information System (INIS)

    Sturm, Stefan; Forsberg, Anton; Stenkrona, Per; Varrone, Andrea; Fazio, Patrik; Nakao, Ryuji; Halldin, Christer; Nave, Stephane; Jamois, Candice; Ricci, Benedicte; Seneca, Nicholas; Comley, Robert A.; Ejduk, Zbigniew; Al-Tawil, Nabil; Akenine, Ulrika; Andreasen, Niels

    2017-01-01

    In Alzheimer's disease (AD), increased metabolism of monoamines by monoamine oxidase type B (MAO-B) leads to the production of toxic reactive oxygen species (ROS), which are thought to contribute to disease pathogenesis. Inhibition of the MAO-B enzyme may restore brain levels of monoaminergic neurotransmitters, reduce the formation of toxic ROS and reduce neuroinflammation (reactive astrocytosis), potentially leading to neuroprotection. Sembragiline (also referred as RO4602522, RG1577 and EVT 302 in previous communications) is a potent, selective and reversible inhibitor of MAO-B developed as a potential treatment for AD. This study assessed the relationship between plasma concentration of sembragiline and brain MAO-B inhibition in patients with AD and in healthy elderly control (EC) subjects. Positron emission tomography (PET) scans using [ 11 C]- L -deprenyl-D 2 radiotracer were performed in ten patients with AD and six EC subjects, who received sembragiline each day for 6-15 days. At steady state, the relationship between sembragiline plasma concentration and MAO-B inhibition resulted in an E max of ∝80-90 % across brain regions of interest and in an EC 50 of 1-2 ng/mL. Data in patients with AD and EC subjects showed that near-maximal inhibition of brain MAO-B was achieved with 1 mg sembragiline daily, regardless of the population, whereas lower doses resulted in lower and variable brain MAO-B inhibition. This PET study confirmed that daily treatment of at least 1 mg sembragiline resulted in near-maximal inhibition of brain MAO-B enzyme in patients with AD. (orig.)

  13. Positron emission tomography measurement of brain MAO-B inhibition in patients with Alzheimer's disease and elderly controls after oral administration of sembragiline

    Energy Technology Data Exchange (ETDEWEB)

    Sturm, Stefan [Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, Basel (Switzerland); F. Hoffmann-La Roche Ltd, Basel (Switzerland); Forsberg, Anton; Stenkrona, Per; Varrone, Andrea; Fazio, Patrik; Nakao, Ryuji; Halldin, Christer [Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatric Research, Stockholm (Sweden); Nave, Stephane; Jamois, Candice; Ricci, Benedicte [Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, Basel (Switzerland); Seneca, Nicholas [AstraZeneca Translational Science Center, Stockholm (Sweden); Comley, Robert A. [AbbVie, North Chicago, IL (United States); Ejduk, Zbigniew [Miedzyleski Specialistic Hospital, Internal Disease and Gastroenterology, Warsaw (Poland); Al-Tawil, Nabil [Karolinska University Hospital, Karolinska Trial Alliance Phase 1 Unit, Stockholm (Sweden); Akenine, Ulrika; Andreasen, Niels [Karolinska University Hospital, Karolinska Institutet Alzheimer Disease Research Centre and Clinical Trial Unit, Geriatric Clinic, Huddinge (Sweden)

    2017-03-15

    In Alzheimer's disease (AD), increased metabolism of monoamines by monoamine oxidase type B (MAO-B) leads to the production of toxic reactive oxygen species (ROS), which are thought to contribute to disease pathogenesis. Inhibition of the MAO-B enzyme may restore brain levels of monoaminergic neurotransmitters, reduce the formation of toxic ROS and reduce neuroinflammation (reactive astrocytosis), potentially leading to neuroprotection. Sembragiline (also referred as RO4602522, RG1577 and EVT 302 in previous communications) is a potent, selective and reversible inhibitor of MAO-B developed as a potential treatment for AD. This study assessed the relationship between plasma concentration of sembragiline and brain MAO-B inhibition in patients with AD and in healthy elderly control (EC) subjects. Positron emission tomography (PET) scans using [{sup 11}C]-{sub L}-deprenyl-D{sub 2} radiotracer were performed in ten patients with AD and six EC subjects, who received sembragiline each day for 6-15 days. At steady state, the relationship between sembragiline plasma concentration and MAO-B inhibition resulted in an E{sub max} of ∝80-90 % across brain regions of interest and in an EC{sub 50} of 1-2 ng/mL. Data in patients with AD and EC subjects showed that near-maximal inhibition of brain MAO-B was achieved with 1 mg sembragiline daily, regardless of the population, whereas lower doses resulted in lower and variable brain MAO-B inhibition. This PET study confirmed that daily treatment of at least 1 mg sembragiline resulted in near-maximal inhibition of brain MAO-B enzyme in patients with AD. (orig.)

  14. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... Copyright © 2018 Alzheimer's Association ® . All rights reserved. Our vision is a world without Alzheimer's Formed in 1980, the Alzheimer's Association is the world's leading voluntary health organization in Alzheimer's care, support and research.

  15. Alzheimer's Disease Mutant Mice Exhibit Reduced Brain Tissue Stiffness Compared to Wild-type Mice in both Normoxia and following Intermittent Hypoxia Mimicking Sleep Apnea.

    Science.gov (United States)

    Menal, Maria José; Jorba, Ignasi; Torres, Marta; Montserrat, Josep M; Gozal, David; Colell, Anna; Piñol-Ripoll, Gerard; Navajas, Daniel; Almendros, Isaac; Farré, Ramon

    2018-01-01

    Evidence from patients and animal models suggests that obstructive sleep apnea (OSA) may increase the risk of Alzheimer's disease (AD) and that AD is associated with reduced brain tissue stiffness. To investigate whether intermittent hypoxia (IH) alters brain cortex tissue stiffness in AD mutant mice exposed to IH mimicking OSA. Six-eight month old (B6C3-Tg(APPswe,PSEN1dE9)85Dbo/J) AD mutant mice and wild-type (WT) littermates were subjected to IH (21% O 2 40 s to 5% O 2 20 s; 6 h/day) or normoxia for 8 weeks. After euthanasia, the stiffness (E) of 200-μm brain cortex slices was measured by atomic force microscopy. Two-way ANOVA indicated significant cortical softening and weight increase in AD mice compared to WT littermates, but no significant effects of IH on cortical stiffness and weight were detected. In addition, reduced myelin was apparent in AD (vs. WT), but no significant differences emerged in the cortex extracellular matrix components laminin and glycosaminoglycans when comparing baseline AD and WT mice. AD mutant mice exhibit reduced brain tissue stiffness following both normoxia and IH mimicking sleep apnea, and such differences are commensurate with increased edema and demyelination in AD.

  16. [Nutritional status in Alzheimer's disease].

    Science.gov (United States)

    Machado, Jacqueline; Caram, Carmen Lucia Barreto; Frank, Andrea Abdala; Soares, Eliane de Abreu; Laks, Jerson

    2009-01-01

    To describe the nutritional status of elderly subjects with mild to moderate Alzheimer's disease. Subjects of both genders (n=40) diagnosed with mild to moderate Alzheimer's disease according to NINCDS-ADRDA criteria, participated in the study. Socioeconomic status, activities of daily life, anthropometric, clinical and dietary profiles were surveyed. Of the total, 65% were female. More than 70% were capable of accomplishing daily activities by themselves. Subjects were eutrophic with a statistically significant difference of the arm circumference between the mild and moderate groups. As for illnesses secondary to Alzheimer's, 52% of the elderly presented hypertension, followed by arthrosis type alterations (17%). The mean consumption of energy and macronutrients in the elderly classified as mild dementia was of 1645 kcal, distributed in 53.7% of carbohydrate, 17.5% of proteins or 0.9 g/kg and 28.8% of lipids. For those classified as moderate dementia it was of 1482 kcal, distributed in 59.3% of carbohydrate, 16.1% of proteins and 24.6% of lipids. In this descriptive study of elderly outpatients with mild and moderate Alzheimer's disease, most presented a nutritional status of eutrophy, with adequate dietary intake of carbohydrates, proteins, lipids and vitamin C, but with low dietary intake of vitamin E.

  17. Alzheimer's disease: studies of diagnosis and therapy

    NARCIS (Netherlands)

    J.J. Claus (Jules Johan)

    1993-01-01

    textabstractDespite tremendous recent advances in the clinical neurology, neurobiology and epidemiology of Alzheimer's disease, the cause as well as its treatment remains as much a mystery today as when it was first described in 1907 by Alois Alzheimer.' Alzheimer's disease, the most common type

  18. Assessing neuronal networks: understanding Alzheimer's disease.

    LENUS (Irish Health Repository)

    Bokde, Arun L W

    2012-02-01

    Findings derived from neuroimaging of the structural and functional organization of the human brain have led to the widely supported hypothesis that neuronal networks of temporally coordinated brain activity across different regional brain structures underpin cognitive function. Failure of integration within a network leads to cognitive dysfunction. The current discussion on Alzheimer\\'s disease (AD) argues that it presents in part a disconnection syndrome. Studies using functional magnetic resonance imaging, positron emission tomography and electroencephalography demonstrate that synchronicity of brain activity is altered in AD and correlates with cognitive deficits. Moreover, recent advances in diffusion tensor imaging have made it possible to track axonal projections across the brain, revealing substantial regional impairment in fiber-tract integrity in AD. Accumulating evidence points towards a network breakdown reflecting disconnection at both the structural and functional system level. The exact relationship among these multiple mechanistic variables and their contribution to cognitive alterations and ultimately decline is yet unknown. Focused research efforts aimed at the integration of both function and structure hold great promise not only in improving our understanding of cognition but also of its characteristic progressive metamorphosis in complex chronic neurodegenerative disorders such as AD.

  19. Progressive Disintegration of Brain Networking from Normal Aging to Alzheimer Disease: Analysis of Independent Components of 18F-FDG PET Data.

    Science.gov (United States)

    Pagani, Marco; Giuliani, Alessandro; Öberg, Johanna; De Carli, Fabrizio; Morbelli, Silvia; Girtler, Nicola; Arnaldi, Dario; Accardo, Jennifer; Bauckneht, Matteo; Bongioanni, Francesca; Chincarini, Andrea; Sambuceti, Gianmario; Jonsson, Cathrine; Nobili, Flavio

    2017-07-01

    Brain connectivity has been assessed in several neurodegenerative disorders investigating the mutual correlations between predetermined regions or nodes. Selective breakdown of brain networks during progression from normal aging to Alzheimer disease dementia (AD) has also been observed. Methods: We implemented independent-component analysis of 18 F-FDG PET data in 5 groups of subjects with cognitive states ranging from normal aging to AD-including mild cognitive impairment (MCI) not converting or converting to AD-to disclose the spatial distribution of the independent components in each cognitive state and their accuracy in discriminating the groups. Results: We could identify spatially distinct independent components in each group, with generation of local circuits increasing proportionally to the severity of the disease. AD-specific independent components first appeared in the late-MCI stage and could discriminate converting MCI and AD from nonconverting MCI with an accuracy of 83.5%. Progressive disintegration of the intrinsic networks from normal aging to MCI to AD was inversely proportional to the conversion time. Conclusion: Independent-component analysis of 18 F-FDG PET data showed a gradual disruption of functional brain connectivity with progression of cognitive decline in AD. This information might be useful as a prognostic aid for individual patients and as a surrogate biomarker in intervention trials. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  20. Structural brain differences between monolingual and multilingual patients with mild cognitive impairment and Alzheimer disease: Evidence for cognitive reserve.

    Science.gov (United States)

    Duncan, Hilary D; Nikelski, Jim; Pilon, Randi; Steffener, Jason; Chertkow, Howard; Phillips, Natalie A

    2018-01-31

    Two independent lines of research provide evidence that speaking more than one language may 1) contribute to increased grey matter in healthy younger and older adults and 2) delay cognitive symptoms in mild cognitive impairment (MCI) or Alzheimer disease (AD). We examined cortical thickness and tissue density in monolingual and multilingual MCI and AD patients matched (within Diagnosis Groups) on demographic and cognitive variables. In medial temporal disease-related (DR) areas, we found higher tissue density in multilingual MCIs versus monolingual MCIs, but similar or lower tissue density in multilingual AD versus monolingual AD, a pattern consistent with cognitive reserve in AD. In areas related to language and cognitive control (LCC), both multilingual MCI and AD patients had thicker cortex than the monolinguals. Results were largely replicated in our native-born Canadian MCI participants, ruling out immigration as a potential confound. Finally, multilingual patients showed a correlation between cortical thickness in LCC regions and performance on episodic memory tasks. Given that multilinguals and monolinguals were matched on memory functioning, this suggests that increased gray matter in these regions may provide support to memory functioning. Our results suggest that being multilingual may contribute to increased gray matter in LCC areas and may also delay the cognitive effects of disease-related atrophy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Different patterns of brain activation in normal aging and Alzheimer's disease from cognitional sight: meta analysis using activation likelihood estimation.

    Science.gov (United States)

    Sadigh-Eteghad, Saeed; Majdi, Alireza; Farhoudi, Mehdi; Talebi, Mahnaz; Mahmoudi, Javad

    2014-08-15

    Alzheimer disease (AD) is a chronic neurological disease, frequently affecting cognitional functions. Recently, a large body of neuro-imaging studies have aimed at finding reliable biomarkers of AD for early diagnosis of disease in contrast with healthy elderlies. We intended to have a meta-analytical study on recent functional neuroimaging studies to find the relationship between cognition in AD patients and normal elderlies. A systematic search was conducted to collect functional neuroimaging studies such as positron emission therapy (PET) and functional magnetic resonance imaging (fMRI) in AD patients and healthy elderlies. The coordinates of regions related to cognition were meta-analyzed using the activation likelihood estimation (ALE) method and Sleuth software. P-value map at the false discovery rate (FDR) of Psize of 200 mm(3) were considered. Data were visualized with MANGO software. Forty-one articles that explored the areas activated during cognition in normal elderly subjects and AD patients were found. According to the findings, left middle frontal gyrus and left precuneus are the most activated areas in cognitional tasks in healthy elderlies and AD patients respectively. In normal elderly subjects and AD patients, comparison of ALE maps and reverse contrast showed that insula and left precuneus were the most activated areas in cognitional aspects respectively. With respect to unification of left precuneus activation in cognitional tasks, it seems that this point can be a hallmark in primary differentiation of AD and healthy individuals. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Is Alzheimer's disease a homogeneous disease entity?

    Science.gov (United States)

    Korczyn, Amos D

    2013-10-01

    The epidemic proportions of dementia in old age are a cause of great concern for the medical profession and the society at large. It is customary to consider Alzheimer's disease (AD) as the most common cause of dementia, and vascular dementia (VaD) as being the second. This dichotomous view of a primary neurodegenerative disease as opposed to a disorder where extrinsic factors cause brain damage led to separate lines of research in these two entities. New biomarkers, particularly the introduction of modern neuroimaging and cerebrospinal fluid changes, have, in recent years, helped to identify anatomical and chemical changes of VaD and of AD. Nevertheless, there is a substantial difference between the two entities. While it is clear that VaD is a heterogeneous entity, AD is supposed to be a single disorder. Nobody attempts to use CADASIL as a template to develops treatment for sporadic VaD. On the other hand, early-onset AD is used to develop therapy for sporadic AD. This paper will discuss the problems relating to this false concept and its consequences.

  3. A 3-Month Aerobic Training Program Improves Brain Energy Metabolism in Mild Alzheimer's Disease: Preliminary Results from a Neuroimaging Study.

    Science.gov (United States)

    Castellano, Christian-Alexandre; Paquet, Nancy; Dionne, Isabelle J; Imbeault, Hélène; Langlois, Francis; Croteau, Etienne; Tremblay, Sébastien; Fortier, Mélanie; Matte, J Jacques; Lacombe, Guy; Fülöp, Tamás; Bocti, Christian; Cunnane, Stephen C

    2017-01-01

    Aerobic training has some benefits for delaying the onset or progression of Alzheimer's disease (AD). Little is known about the implication of the brain's two main fuels, glucose and ketones (acetoacetate), associated with thesebenefits. To determine whether aerobic exercise training modifies brain energy metabolism in mild AD. In this uncontrolled study, ten patients with mild AD participated in a 3-month, individualized, moderate-intensity aerobic training on a treadmill (Walking). Quantitative measurement of brain uptake of glucose (CMRglu) and acetoacetate (CMRacac) using neuroimaging and cognitive testing were done before and after the Walking program. Four men and six women with an average global cognitive score (MMSE) of 26/30 and an average age of 73 y completed the Walking program. Average total distance and treadmill speed were 8 km/week and 4 km/h, respectively. Compared to the Baseline, after Walking, CMRacac was three-fold higher (0.6±0.4 versus 0.2±0.1 μmol/100 g/min; p = 0.01). Plasma acetoacetate concentration and the blood-to-brain acetoacetate influx rate constant were also increased by 2-3-fold (all p≤0.03). CMRglu was unchanged after Walking (28.0±0.1 μmol/100 g/min; p = 0.96). There was a tendency toward improvement in the Stroop-color naming test (-10% completion time, p = 0.06). Performance on the Trail Making A&B tests was also directly related to plasma acetoacetate and CMRacac (all p≤0.01). In mild AD, aerobic training improved brain energy metabolism by increasing ketone uptake and utilization while maintaining brain glucose uptake, and could potentially be associated with some cognitive improvement.

  4. Potential of the Antibody Against cis-Phosphorylated Tau in the Early Diagnosis, Treatment, and Prevention of Alzheimer Disease and Brain Injury.

    Science.gov (United States)

    Lu, Kun Ping; Kondo, Asami; Albayram, Onder; Herbert, Megan K; Liu, Hekun; Zhou, Xiao Zhen

    2016-11-01

    Alzheimer disease (AD) and chronic traumatic encephalopathy (CTE) share a common neuropathologic signature-neurofibrillary tangles made of phosphorylated tau-but do not have the same pathogenesis or symptoms. Although whether traumatic brain injury (TBI) could cause AD has not been established, CTE is shown to be associated with TBI. Until recently, whether and how TBI leads to tau-mediated neurodegeneration was unknown. The unique prolyl isomerase Pin1 protects against the development of tau-mediated neurodegeneration in AD by converting the phosphorylated Thr231-Pro motif in tau (ptau) from the pathogenic cis conformation to the physiologic trans conformation, thereby restoring ptau function. The recent development of antibodies able to distinguish and eliminate both conformations specifically has led to the discovery of cis-ptau as a precursor of tau-induced pathologic change and an early driver of neurodegeneration that directly links TBI to CTE and possibly to AD. Within hours of TBI in mice or neuronal stress in vitro, neurons prominently produce cis-ptau, which causes and spreads cis-ptau pathologic changes, termed cistauosis. Cistauosis eventually leads to widespread tau-mediated neurodegeneration and brain atrophy. Cistauosis is effectively blocked by the cis-ptau antibody, which targets intracellular cis-ptau for proteasome-mediated degradation and prevents extracellular cis-ptau from spreading to other neurons. Treating TBI mice with cis-ptau antibody not only blocks early cistauosis but also prevents development and spreading of tau-mediated neurodegeneration and brain atrophy and restores brain histopathologic features and functional outcomes. Thus, cistauosis is a common early disease mechanism for AD, TBI, and CTE, and cis-ptau and its antibody may be useful for early diagnosis, treatment, and prevention of these devastating diseases.

  5. Prebiotic Effect of Fructooligosaccharides fromMorinda officinalison Alzheimer's Disease in Rodent Models by Targeting the Microbiota-Gut-Brain Axis.

    Science.gov (United States)

    Chen, Diling; Yang, Xin; Yang, Jian; Lai, Guoxiao; Yong, Tianqiao; Tang, Xiaocui; Shuai, Ou; Zhou, Gailian; Xie, Yizhen; Wu, Qingping

    2017-01-01

    Gut microbiota influences the central nervous system disorders such as Alzheimer's disease (AD). The prebiotics and probiotics can improve the host cognition. A previous study demonstrated that fructooligosaccharides from Morinda officinalis (OMO) exert effective memory improvements in AD-like animals, thereby considered as potential prebiotics; however, the underlying mechanism still remains enigma. Thus, the present study investigated whether OMO is effective in alleviating AD by targeting the microbiota-gut-brain axis. OMO was administered in rats with AD-like symptoms (D-galactose- and Aβ 1-42 -induced deficient rats). Significant and systematic deterioration in AD-like animals were identified, including learning and memory abilities, histological changes, production of cytokines, and microbial community shifts. Behavioral experiments demonstrated that OMO administration can ameliorate the learning and memory abilities in both AD-like animals significantly. AD parameters showed that OMO administration cannot only improve oxidative stress and inflammation disorder, but also regulate the synthesis and secretion of neurotransmitter. Histological changes indicated that OMO administration ameliorates the swelling of brain tissues, neuronal apoptosis, and down-regulation of the expression of AD intracellular markers (Tau and Aβ 1-42 ). 16S rRNA sequencing of gut microbiota indicated that OMO administration maintains the diversity and stability of the microbial community. In addition, OMO regulated the composition and metabolism of gut microbiota in inflammatory bowel disease (IBD) mice model treated by overdosed antibiotics and thus showed the prebiotic potential. Moreover, gut microbiota plays a major role in neurodevelopment, leading to alterations in gene expression in critical brain and intestinal regions, thereby resulting in perturbation to the programming of normal cognitive behaviors. Taken together, our findings suggest that the therapeutic effect of the

  6. How Alzheimer's Changes the Brain

    Medline Plus

    Full Text Available ... 4-minute video shows how Alzheimer’s affects the human brain and looks at promising ideas to treat ... views 2:29 The resistant brain: nourishing our bodies against Alzheimer’s | Owen Carmichael | TEDxLSU - Duration: 12:17. ...

  7. How Alzheimer's Changes the Brain

    Medline Plus

    Full Text Available ... 4-minute video shows how Alzheimer’s affects the human brain and looks at promising ideas to treat ... 1:13:27 The resistant brain: nourishing our bodies against Alzheimer’s | Owen Carmichael | TEDxLSU - Duration: 12:17. ...

  8. Systemic inflammation, blood-brain barrier vulnerability and cognitive / non-cognitive symptoms in Alzheimer disease: Relevance to pathogenesis and therapy

    Directory of Open Access Journals (Sweden)

    Shuko eTakeda

    2014-07-01

    Full Text Available The incidence of dementia is increasing at an alarming rate, and has become a major public health concern. Alzheimer disease (AD is the most common form of dementia and is characterized by progressive cognitive impairment. In addition to classical neuropathological features such as amyloid plaques and neurofibrillary tangles, accumulation of activated immune cells has been documented in the AD brain, suggesting a contribution of neuroinflammation in the pathogenesis of AD. Besides cognitive deterioration, non-cognitive symptoms, such as agitation, aggression, depression and psychosis, are often observed in demented patients, including those with AD, and these neuropsychological symptoms place a heavy burden on caregivers. These symptoms often exhibit sudden onset and tend to fluctuate over time, and in many cases, they are triggered by an infection in peripheral organs, suggesting that inflammation plays an important role in the pathogenesis of these non-cognitive symptoms. However, there is no mechanistic explanation for the relationship between inflammation and neuropsychiatric symptoms. Observations from experimental mouse models indicate that alteration of brain blood vessels, especially blood-brain barrier dysfunction, may contribute to the relationship. The current review summarizes the results from recent studies on the relationship between inflammation and AD, while focusing on cerebrovascular alterations, which might provide an insight into the pathogenesis of cognitive / non-cognitive symptoms in AD patients and suggest a basis for the development of new therapeutic treatments for these conditions.

  9. Characterization of Proteins Present in Isolated Senile Plaques from Alzheimer's Diseased Brains by MALDI-TOF MS with MS/MS.

    Science.gov (United States)

    Kelley, Andrea R; Perry, George; Bach, Stephan B H

    2018-04-18

    The increase of insoluble senile plaques in the brain is a primary hallmark of Alzheimer's disease. The usefulness of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with tandem MS for the characterization of senile plaques from AD brains and the relevance of the components identified to furthering AD research using MS is discussed. Thirty-three components were reproducibly observed within tryptic aliquots of senile plaques from two different AD brains after sample preparation optimization. Additionally, this is one of the first accounts of LIFT being utilized for the direct sequencing of peptides from isolated senile plaques. While many of the species observed coisolated within senile plaques have been linked to AD etiology, if only speculatively, this is the first instance that many of them have been demonstrated to be a part of the plaques themselves. This work is the first step in determining the potential roles that the species may have in the aggregation or proliferation of the plaques.

  10. Differing associations between Aβ accumulation, hypoperfusion, blood-brain barrier dysfunction and loss of PDGFRB pericyte marker in the precuneus and parietal white matter in Alzheimer's disease.

    Science.gov (United States)

    Miners, J Scott; Schulz, Isabel; Love, Seth

    2018-01-01

    Recent studies implicate loss of pericytes in hypoperfusion and blood-brain barrier (BBB) leakage in Alzheimer's disease (AD). In this study, we have measured levels of the pericyte marker, platelet-derived growth factor receptor-β (PDGFRB), and fibrinogen (to assess blood-brain barrier leakage), and analyzed their relationship to indicators of microvessel density (von Willebrand factor level), ante-mortem oxygenation (myelin-associated glycoprotein:proteolipid protein-1 ratio and vascular endothelial growth factor level), Aβ level and plaque load, in precuneus and underlying white matter from 49 AD to 37 control brains. There was reduction in PDGFRB and increased fibrinogen in the precuneus in AD. These changes correlated with reduction in oxygenation and with plaque load. In the underlying white matter, increased fibrinogen correlated with reduced oxygenation, but PDGFRB level was unchanged. The level of platelet-derived growth factor-ββ (PDGF-BB), important for pericyte maintenance, was increased in AD but mainly in the insoluble tissue fraction, correlating with insoluble Aβ level. Loss of the PDGFRB within the precuneus in AD is associated with fibrinogen leakage and reduced oxygenation, and related to fibrillar Aβ accumulation. In contrast, fibrinogen leakage and reduced oxygenation of underlying white matter occur independently of loss of PDGFRB, perhaps secondary to reduced transcortical perfusion.

  11. Cognitive and neuroimaging features and brain β-amyloidosis in individuals at risk of Alzheimer's disease (INSIGHT-preAD): a longitudinal observational study.

    Science.gov (United States)

    Dubois, Bruno; Epelbaum, Stephane; Nyasse, Francis; Bakardjian, Hovagim; Gagliardi, Geoffroy; Uspenskaya, Olga; Houot, Marion; Lista, Simone; Cacciamani, Federica; Potier, Marie-Claude; Bertrand, Anne; Lamari, Foudil; Benali, Habib; Mangin, Jean-François; Colliot, Olivier; Genthon, Remy; Habert, Marie-Odile; Hampel, Harald

    2018-04-01

    Improved understanding is needed of risk factors and markers of disease progression in preclinical Alzheimer's disease. We assessed associations between brain β-amyloidosis and various cognitive and neuroimaging parameters with progression of cognitive decline in individuals with preclinical Alzheimer's disease. The INSIGHT-preAD is an ongoing single-centre observational study at the Salpêtrière Hospital, Paris, France. Eligible participants were age 70-85 years with subjective memory complaints but unimpaired cognition and memory (Mini-Mental State Examination [MMSE] score ≥27, Clinical Dementia Rating score 0, and Free and Cued Selective Reminding Test [FCSRT] total recall score ≥41). We stratified participants by brain amyloid β deposition on 18 F-florbetapir PET (positive or negative) at baseline. All patients underwent baseline assessments of demographic, cognitive, and psychobehavioural, characteristics, APOE ε4 allele carrier status, brain structure and function on MRI, brain glucose-metabolism on 18 F-fluorodeoxyglucose ( 18 F-FDG) PET, and event-related potentials on electroencephalograms (EEGs). Actigraphy and CSF investigations were optional. Participants were followed up with clinical, cognitive, and psychobehavioural assessments every 6 months, neuropsychological assessments, EEG, and actigraphy every 12 months, and MRI, and 18 F-FDG and 18 F-florbetapir PET every 24 months. We assessed associations of amyloid β deposition status with test outcomes at baseline and 24 months, and with clinical status at 30 months. Progression to prodromal Alzheimer's disease was defined as an amnestic syndrome of the hippocampal type. From May 25, 2013, to Jan 20, 2015, we enrolled 318 participants with a mean age of 76·0 years (SD 3·5). The mean baseline MMSE score was 28·67 (SD 0·96), and the mean level of education was high (score >6 [SD 2] on a scale of 1-8, where 1=infant school and 8=higher education). 88 (28%) of 318 participants showed amyloid

  12. Quantitation, regional vulnerability, and kinetic modeling of brain glucose metabolism in mild Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Mosconi, Lisa; Rusinek, Henry; De Santi, Susan; Li, Yi [New York University School of Medicine, Center for Brain Health, MHL 400, Department of Psychiatry, New York, NY (United States); Tsui, Wai H.; De Leon, Mony J. [New York University School of Medicine, Center for Brain Health, MHL 400, Department of Psychiatry, New York, NY (United States); Nathan Kline Institute, Orangeburg, NY (United States); Wang, Gene-Jack; Fowler, Joanna [Brookhaven National Laboratory, Upton, NY (United States); Pupi, Alberto [University of Florence, Department of Clinical Pathophysiology, Nuclear Medicine Unit, Florence (Italy)

    2007-09-15

    To examine CMRglc measures and corresponding glucose transport (K{sub 1} and k{sub 2}) and phosphorylation (k{sub 3}) rates in the medial temporal lobe (MTL, comprising the hippocampus and amygdala) and posterior cingulate cortex (PCC) in mild Alzheimer's disease (AD). Dynamic FDG PET with arterial blood sampling was performed in seven mild AD patients (age 68 {+-} 8 years, four females, median MMSE 23) and six normal (NL) elderly (age 69 {+-} 9 years, three females, median MMSE 30). Absolute CMRglc ({mu}mol/100 g/min) was calculated from MRI-defined regions of interest using multiparametric analysis with individually fitted kinetic rate constants, Gjedde-Patlak plot, and Sokoloff's autoradiographic method with population-based rate constants. Relative ROI/pons CMRglc (unitless) was also examined. With all methods, AD patients showed significant CMRglc reductions in the hippocampus and PCC, and a trend towards reduced parietotemporal CMRglc, as compared with NL. Significant k{sub 3} reductions were found in the hippocampus, PCC and amygdala. K{sub 1} reductions were restricted to the hippocampus. Relative CMRglc had the largest effect sizes in separating AD from NL. However, the magnitude of CMRglc reductions was 1.2- to 1.9-fold greater with absolute than with relative measures. CMRglc reductions are most prominent in the MTL and PCC in mild AD, as detected with both absolute and relative CMRglc measures. Results are discussed in terms of clinical and pharmaceutical applicability. (orig.)

  13. Report by the Spanish Foundation of the Brain on the social impact of Alzheimer disease and other types of dementia.

    Science.gov (United States)

    Villarejo Galende, A; Eimil Ortiz, M; Llamas Velasco, S; Llanero Luque, M; López de Silanes de Miguel, C; Prieto Jurczynska, C

    2017-12-14

    Knowledge of the socioeconomic impact of dementia-related disorders is essential for appropriate management of healthcare resources and for raising social awareness. We performed a literature review of the published evidence on the epidemiology, morbidity, mortality, associated disability and dependence, and economic impact of dementia and Alzheimer disease (AD) in Spain. Most population studies of patients older than 65 report prevalence rates ranging from 4% to 9%. Prevalence of dementia and AD is higher in women for nearly every age group. AD is the most common cause of dementia (50%-70% of all cases). Dementia is associated with increased morbidity, mortality, disability, and dependence, and results in a considerable decrease in quality of life and survival. Around 80% of all patients with dementia are cared for by their families, which cover a mean of 87% of the total economic cost, resulting in considerable economic and health burden on caregivers and loss of quality of life. The economic impact of dementia is huge and difficult to evaluate due to the combination of direct and indirect costs. More comprehensive programmes should be developed and resources dedicated to research, prevention, early diagnosis, multidimensional treatment, and multidisciplinary management of these patients in order to reduce the health, social, and economic burden of dementia. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. How Alzheimer's Changes the Brain

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    Full Text Available ... has been rented. This feature is not available right now. Please try again later. Published on Aug ... Your Brain Healthy for the Rest of Your Life - Duration: 57:30. University of California Television (UCTV) ...

  15. A novel blood-brain barrier co-culture system for drug targeting of Alzheimer's disease: establishment by using acitretin as a model drug.

    Directory of Open Access Journals (Sweden)

    Christian Freese

    Full Text Available In the pathogenesis of Alzheimer's disease (AD the homeostasis of amyloid precursor protein (APP processing in the brain is impaired. The expression of the competing proteases ADAM10 (a disintegrin and metalloproteinase 10 and BACE-1 (beta site APP cleaving enzyme 1 is shifted in favor of the A-beta generating enzyme BACE-1. Acitretin--a synthetic retinoid-e.g., has been shown to increase ADAM10 gene expression, resulting in a decreased level of A-beta peptides within the brain of AD model mice and thus is of possible value for AD therapy. A striking challenge in evaluating novel therapeutically applicable drugs is the analysis of their potential to overcome the blood-brain barrier (BBB for central nervous system targeting. In this study, we established a novel cell-based bio-assay model to test ADAM10-inducing drugs for their ability to cross the BBB. We therefore used primary porcine brain endothelial cells (PBECs and human neuroblastoma cells (SH-SY5Y transfected with an ADAM10-promoter luciferase reporter vector in an indirect co-culture system. Acitretin served as a model substance that crosses the BBB and induces ADAM10 expression. We ensured that ADAM10-dependent constitutive APP metabolism in the neuronal cells was unaffected under co-cultivation conditions. Barrier properties established by PBECs were augmented by co-cultivation with SH-SY5Y cells and they remained stable during the treatment with acitretin as demonstrated by electrical resistance measurement and permeability-coefficient determination. As a consequence of transcellular acitretin transport measured by HPLC, the activity of the ADAM10-promoter reporter gene was significantly increased in co-cultured neuronal cells as compared to vehicle-treated controls. In the present study, we provide a new bio-assay system relevant for the study of drug targeting of AD. This bio-assay can easily be adapted to analyze other Alzheimer- or CNS disease-relevant targets in neuronal cells

  16. Evaluation of brain perfusion in specific Brodmann areas in Frontotemporal dementia and Alzheimer disease using automated 3-D voxel based analysis

    Science.gov (United States)

    Valotassiou, V.; Papatriantafyllou, J.; Sifakis, N.; Karageorgiou, C.; Tsougos, I.; Tzavara, C.; Zerva, C.; Georgoulias, P.

    2009-05-01

    Introduction. Brain perfusion studies with single-photon emission computed tomography (SPECT) have been applied in demented patients to provide better discrimination between frontotemporal dementia (FTD) and Alzheimer's disease (AD). Aim. To assess the perfusion of specific Brodmann (Br) areas of the brain cortex in FTD and AD patients, using NeuroGam processing program to provide 3D voxel-by-voxel cerebral SPECT analysis. Material and methods. We studied 34 consecutive patients. We used the established criteria for the diagnosis of dementia and the specific established criteria for the diagnosis of FTD and AD. All the patients had a neuropsychological evaluation with a battery of tests including the mini-mental state examination (MMSE).Twenty-six patients (16 males, 10 females, mean age 68.76±6.51 years, education 11.81±4.25 years, MMSE 16.69±9.89) received the diagnosis of FTD and 8 patients (all females, mean age 71.25±10.48 years, education 10±4.6 years, MMSE 12.5±3.89) the diagnosis of AD. All the patients underwent a brain SPECT. We applied the NeuroGam Software for the evaluation of brain perfusion in specific Br areas in the left (L) and right (R) hemispheres. Results. Statistically significant hypoperfusion in FTD compared to AD patients, was found in the following Br areas: 11L (pareas. Conclusion. NeuroGam processing program of brain perfusion SPECT could result in enhanced accuracy for the differential diagnosis between AD and FTD patients.

  17. Evaluation of brain perfusion in specific Brodmann areas in Frontotemporal dementia and Alzheimer disease using automated 3-D voxel based analysis

    Energy Technology Data Exchange (ETDEWEB)

    Valotassiou, V; Tsougos, I; Tzavara, C; Georgoulias, P [Nuclear Medicine Dpt, University Hospital of Larissa, Larissa (Greece); Papatriantafyllou, J; Karageorgiou, C [Neurology Dpt, General Hospital ' G. Gennimatas' , Athens (Greece); Sifakis, N; Zerva, C [Nuclear Medicine Dpt, ' Alexandra' University Hospital, Athens (Greece)], E-mail: vanvalot@yahoo.gr

    2009-05-15

    Introduction. Brain perfusion studies with single-photon emission computed tomography (SPECT) have been applied in demented patients to provide better discrimination between frontotemporal dementia (FTD) and Alzheimer's disease (AD). Aim. To assess the perfusion of specific Brodmann (Br) areas of the brain cortex in FTD and AD patients, using NeuroGam processing program to provide 3D voxel-by-voxel cerebral SPECT analysis. Material and methods. We studied 34 consecutive patients. We used the established criteria for the diagnosis of dementia and the specific established criteria for the diagnosis of FTD and AD. All the patients had a neuropsychological evaluation with a battery of tests including the mini-mental state examination (MMSE).Twenty-six patients (16 males, 10 females, mean age 68.76{+-}6.51 years, education 11.81{+-}4.25 years, MMSE 16.69{+-}9.89) received the diagnosis of FTD and 8 patients (all females, mean age 71.25{+-}10.48 years, education 10{+-}4.6 years, MMSE 12.5{+-}3.89) the diagnosis of AD. All the patients underwent a brain SPECT. We applied the NeuroGam Software for the evaluation of brain perfusion in specific Br areas in the left (L) and right (R) hemispheres. Results. Statistically significant hypoperfusion in FTD compared to AD patients, was found in the following Br areas: 11L (p<0.0001), 11R, 20L, 20R, 32L, 38L, 38R, 44L (p<0.001), 32R, 36L, 36R, 45L, 45R, 47R (p<0.01), 9L, 21L, 39R, 44R, 46R, 47L (p<0.05). On the contrary, AD patients presented significant (p<0.05) hypoperfusion in 7R and 39R Br areas. Conclusion. NeuroGam processing program of brain perfusion SPECT could result in enhanced accuracy for the differential diagnosis between AD and FTD patients.

  18. Functional disorganization of small-world brain networks in mild Alzheimer's Disease and amnestic Mild Cognitive Impairment: an EEG study using Relative Wavelet Entropy (RWE).

    Science.gov (United States)

    Frantzidis, Christos A; Vivas, Ana B; Tsolaki, Anthoula; Klados, Manousos A; Tsolaki, Magda; Bamidis, Panagiotis D

    2014-01-01

    Previous neuroscientific findings have linked Alzheimer's Disease (AD) with less efficient information processing and brain network disorganization. However, pathological alterations of the brain networks during the preclinical phase of amnestic Mild Cognitive Impairment (aMCI) remain largely unknown. The present study aimed at comparing patterns of the detection of functional disorganization in MCI relative to Mild Dementia (MD). Participants consisted of 23 cognitively healthy adults, 17 aMCI and 24 mild AD patients who underwent electroencephalographic (EEG) data acquisition during a resting-state condition. Synchronization analysis through the Orthogonal Discrete Wavelet Transform (ODWT), and directional brain network analysis were applied on the EEG data. This computational model was performed for networks that have the same number of edges (N = 500, 600, 700, 800 edges) across all participants and groups (fixed density values). All groups exhibited a small-world (SW) brain architecture. However, we found a significant reduction in the SW brain architecture in both aMCI and MD patients relative to the group of Healthy controls. This functional disorganization was also correlated with the participant's generic cognitive status. The deterioration of the network's organization was caused mainly by deficient local information processing as quantified by the mean cluster coefficient value. Functional hubs were identified through the normalized betweenness centrality metric. Analysis of the local characteristics showed relative hub preservation even with statistically significant reduced strength. Compensatory phenomena were also evident through the formation of additional hubs on left frontal and parietal regions. Our results indicate a declined functional network organization even during the prodromal phase. Degeneration is evident even in the preclinical phase and coexists with transient network reorganization due to compensation.

  19. Differential Effects of Structural Modifications on the Competition of Chalcones for the PIB Amyloid Imaging Ligand-Binding Site in Alzheimer's Disease Brain and Synthetic Aβ Fibrils.

    Science.gov (United States)

    Fosso, Marina Y; McCarty, Katie; Head, Elizabeth; Garneau-Tsodikova, Sylvie; LeVine, Harry

    2016-02-17

    Alzheimer's disease (AD) is a complex brain disorder that still remains ill defined. In order to understand the significance of binding of different clinical in vivo imaging ligands to the polymorphic pathological features of AD brain, the molecular characteristics of the ligand interacting with its specific binding site need to be defined. Herein, we observed that tritiated Pittsburgh Compound B ((3)H-PIB) can be displaced from synthetic Aβ(1-40) and Aβ(1-42) fibrils and from the PIB binding complex purified from human AD brain (ADPBC) by molecules containing a chalcone structural scaffold. We evaluated how substitution on the chalcone scaffold alters its ability to displace (3)H-PIB from the synthetic fibrils and ADPBC. By comparing unsubstituted core chalcone scaffolds along with the effects of bromine and methyl substitution at various positions, we found that attaching a hydroxyl group on the ring adjacent to the carbonyl group (ring I) of the parent member of the chalcone family generally improved the binding affinity of chalcones toward ADPBC and synthetic fibrils F40 and F42. Furthermore, any substitution on ring I at the ortho-position of the carbonyl group greatly decreases the binding affinity of the chalcones, potentially as a result of steric hindrance. Together with the finding that neither our chalcones nor PIB interact with the Congo Red/X-34 binding site, these molecules provide new tools to selectively probe the PIB binding site that is found in human AD brain, but not in brains of AD pathology animal models. Our chalcone derivatives also provide important information on the effects of fibril polymorphism on ligand binding.

  20. Selecting the most relevant brain regions to discriminate Alzheimer's disease patients from healthy controls using multiple kernel learning: A comparison across functional and structural imaging modalities and atlases.

    Science.gov (United States)

    Rondina, Jane Maryam; Ferreira, Luiz Kobuti; de Souza Duran, Fabio Luis; Kubo, Rodrigo; Ono, Carla Rachel; Leite, Claudia Costa; Smid, Jerusa; Nitrini, Ricardo; Buchpiguel, Carlos Alberto; Busatto, Geraldo F

    2018-01-01

    Machine learning techniques such as support vector machine (SVM) have been applied recently in order to accurately classify individuals with neuropsychiatric disorders such as Alzheimer's disease (AD) based on neuroimaging data. However, the multivariate nature of the SVM approach often precludes the identification of the brain regions that contribute most to classification accuracy. Multiple kernel learning (MKL) is a sparse machine learning method that allows the identification of the most relevant sources for the classification. By parcelating the brain into regions of interest (ROI) it is possible to use each ROI as a source to MKL (ROI-MKL). We applied MKL to multimodal neuroimaging data in order to: 1) compare the diagnostic performance of ROI-MKL and whole-brain SVM in discriminating patients with AD from demographically matched healthy controls and 2) identify the most relevant brain regions to the classification. We used two atlases (AAL and Brodmann's) to parcelate the brain into ROIs and applied ROI-MKL to structural (T1) MRI, 18 F-FDG-PET and regional cerebral blood flow SPECT (rCBF-SPECT) data acquired from the same subjects (20 patients with early AD and 18 controls). In ROI-MKL, each ROI received a weight (ROI-weight) that indicated the region's relevance to the classification. For each ROI, we also calculated whether there was a predominance of voxels indicating decreased or increased regional activity (for 18 F-FDG-PET and rCBF-SPECT) or volume (for T1-MRI) in AD patients. Compared to whole-brain SVM, the ROI-MKL approach resulted in better accuracies (with either atlas) for classification using 18 F-FDG-PET (92.5% accuracy for ROI-MKL versus 84% for whole-brain), but not when using rCBF-SPECT or T1-MRI. Although several cortical and subcortical regions contributed to discrimination, high ROI-weights and predominance of hypometabolism and atrophy were identified specially in medial parietal and temporo-limbic cortical regions. Also, the weight of

  1. Depression and Alzheimer's Disease

    Science.gov (United States)

    ... help them—and you—feel better. As the caregiver of a person who has Alzheimer’s disease, you must also take care of yourself. If ... that is given to a patient who has Alzheimer’s disease in order to provide relief for the caregiver. Look or ask the doctor for caregiver support ...

  2. Alzheimer's Disease Facts and Figures

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    Full Text Available ... is a not-for-profit 501(c)(3) organization. Copyright © 2018 Alzheimer's Association ® . All rights reserved. Our ... Alzheimer's Association is the world's leading voluntary health organization in Alzheimer's care, support and research.

  3. Alzheimer's Disease Facts and Figures

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    Full Text Available ... a rate twice as high. Invest in a world without Alzheimer's. Donate Caregivers In 2016, 15.9 ... Association ® . All rights reserved. Our vision is a world without Alzheimer's Formed in 1980, the Alzheimer's Association ...

  4. Alzheimer's Disease Facts and Figures

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    Full Text Available ... a rate twice as high. Invest in a world without Alzheimer's. Donate Caregivers Eighty-three percent of ... Association ® . All rights reserved. Our vision is a world without Alzheimer's Formed in 1980, the Alzheimer's Association ...

  5. Alzheimer's Disease Facts and Figures

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    Full Text Available ... In My Area | Alzheimer's & Dementia | Life with ALZ | Research | Professionals | We Can Help | Join the Cause alz. ... news and advances in Alzheimer's treatments, care and research. Get tips for living with Alzheimer's as well ...

  6. Networks of tau distribution in Alzheimer's disease.

    Science.gov (United States)

    Hoenig, Merle C; Bischof, Gérard N; Seemiller, Joseph; Hammes, Jochen; Kukolja, Juraj; Onur, Özgür A; Jessen, Frank; Fliessbach, Klaus; Neumaier, Bernd; Fink, Gereon R; van Eimeren, Thilo; Drzezga, Alexander

    2018-02-01

    See Whitwell (doi:10.1093/brain/awy001) for a scientific commentary on this article.A stereotypical anatomical propagation of tau pathology has been described in Alzheimer's disease. According to recent concepts (network degeneration hypothesis), this propagation is thought to be indicative of misfolded tau proteins possibly spreading along functional networks. If true, tau pathology accumulation should correlate in functionally connected brain regions. Therefore, we examined whether independent components could be identified in the distribution pattern of in vivo tau pathology and whether these components correspond with specific functional connectivity networks. Twenty-two 18F-AV-1451 PET scans of patients with amnestic Alzheimer's disease (mean age = 66.00 ± 7.22 years, 14 males/eight females) were spatially normalized, intensity standardized to the cerebellum, and z-transformed using the mean and deviation image of a healthy control sample to assess Alzheimer's disease-related tau pathology. First, to detect distinct tau pathology networks, the deviation maps were subjected to an independent component analysis. Second, to investigate if regions of high tau burden are associated with functional connectivity networks, we extracted the region with the maximum z-value in each of the generated tau pathology networks and used them as seeds in a subsequent resting-state functional MRI analysis, conducted in a group of healthy adults (n = 26) who were part of the 1000 Functional Connectomes Project. Third, to examine if tau pathology co-localizes with functional connectivity networks, we quantified the spatial overlap between the seed-based networks and the corresponding tau pathology network by calculating the Dice similarity coefficient. Additionally, we assessed if the tau-dependent seed-based networks correspond with known functional resting-state networks. Finally, we examined the relevance of the identified components in regard to the neuropathological Braak

  7. A novel p38α MAPK inhibitor suppresses brain proinflammatory cytokine up-regulation and attenuates synaptic dysfunction and behavioral deficits in an Alzheimer's disease mouse model

    Directory of Open Access Journals (Sweden)

    McNamara Laurie K

    2007-09-01

    Full Text Available Abstract Background An accumulating body of evidence is consistent with the hypothesis that excessive or prolonged increases in proinflammatory cytokine production by activated glia is a contributor to the progression of pathophysiology that is causally linked to synaptic dysfunction and hippocampal behavior deficits in neurodegenerative diseases such as Alzheimer's disease (AD. This raises the opportunity for the development of new classes of potentially disease-modifying therapeutics. A logical candidate CNS target is p38α MAPK, a well-established drug discovery molecular target for altering proinflammatory cytokine cascades in peripheral tissue disorders. Activated p38 MAPK is seen in human AD brain tissue and in AD-relevant animal models, and cell culture studies strongly implicate p38 MAPK in the increased production of proinflammatory cytokines by glia activated with human amyloid-beta (Aβ and other disease-relevant stressors. However, the vast majority of small molecule drugs do not have sufficient penetrance of the blood-brain barrier to allow their use as in vivo research tools or as therapeutics for neurodegenerative disorders. The goal of this study was to test the hypothesis that brain p38α MAPK is a potential in vivo target for orally bioavailable, small molecules capable of suppressing excessive cytokine production by activated glia back towards homeostasis, allowing an improvement in neurologic outcomes. Methods A novel synthetic small molecule based on a molecular scaffold used previously was designed, synthesized, and subjected to analyses to demonstrate its potential in vivo bioavailability, metabolic stability, safety and brain uptake. Testing for in vivo efficacy used an AD-relevant mouse model. Results A novel, CNS-penetrant, non-toxic, orally bioavailable, small molecule inhibitor of p38α MAPK (MW01-2-069A-SRM was developed. Oral administration of the compound at a low dose (2.5 mg/kg resulted in attenuation of

  8. Advances in Raman spectroscopy for the diagnosis of Alzheimer's disease

    Science.gov (United States)

    Sudworth, Caroline D.; Archer, John K. J.; Black, Richard A.; Mann, David

    2006-02-01

    Within the next 50 years Alzheimer's disease is expected to affect 100 million people worldwide. The progressive decline in the mental health of the patient is caused by severe brain atrophy generated by the breakdown and aggregation of proteins, resulting in β-amyloid plaques and neurofibrillary tangles. The greatest challenge to Alzheimer's disease lies in the pursuit of an early and definitive diagnosis, in order that suitable treatment can be administered. At the present time, definitive diagnosis is restricted to post-mortem examination. Alzheimer's disease also remains without a long-term cure. This research demonstrates the potential role of Raman spectroscopy, combined with principle components analysis (PCA), as a diagnostic method. Analyses of ethically approved ex vivo post-mortem brain tissues (originating from frontal and occipital lobes) from control (3 normal elderly subjects and 3 Huntingdon's disease subjects) and Alzheimer's disease (12 subjects) brain sections, and a further set of 12 blinded samples are presented. Spectra originating from these tissues are highly reproducible, and initial results indicate a vital difference in protein content and conformation, relating to the abnormally high levels of aggregated proteins in the diseased tissues. Further examination of these spectra using PCA allows for the separation of control from diseased tissues. The validation of the PCA models using blinded samples also displays promise for the identification of Alzheimer's disease, in conjunction with secondary information regarding other brain diseases and dementias. These results provide a route for Raman spectroscopy as a possible non-invasive, non-destructive tool for the early diagnosis of Alzheimer's disease.

  9. Distress and Coping among Caregivers of Victims of Alzheimer's Disease.

    Science.gov (United States)

    Dundon, Margaret M.; And Others

    Alzheimer's disease is an insidious, progressively destructive brain disease which leads to the loss of judgment, communication skills, and psychomotor control preventing the victim from living independently. The consequences of caring for victims include emotional, physical, and familial strain as the caregiver is faced with the progressive…

  10. Corpus callosum atrophy in patients with mild Alzheimer's disease

    DEFF Research Database (Denmark)

    Frederiksen, Kristian Steen; Garde, Ellen; Skimminge, Arnold

    2011-01-01

    Several studies have found atrophy of the corpus callosum (CC) in patients with Alzheimer's disease (AD). However, it remains unclear whether callosal atrophy is already present in the early stages of AD, and to what extent it may be associated with other structural changes in the brain......, such as age-related white matter changes (ARWMC) and progression of the disease....

  11. Amyloid beta peptide immunotherapy in Alzheimer disease.

    Science.gov (United States)

    Delrieu, J; Ousset, P J; Voisin, T; Vellas, B

    2014-12-01

    Recent advances in the understanding of Alzheimer's disease pathogenesis have led to the development of numerous compounds that might modify the disease process. Amyloid β peptide represents an important molecular target for intervention in Alzheimer's disease. The main purpose of this work is to review immunotherapy studies in relation to the Alzheimer's disease. Several types of amyloid β peptide immunotherapy for Alzheimer's disease are under investigation, active immunization and passive administration with monoclonal antibodies directed against amyloid β peptide. Although immunotherapy approaches resulted in clearance of amyloid plaques in patients with Alzheimer's disease, this clearance did not show significant cognitive effect for the moment. Currently, several amyloid β peptide immunotherapy approaches are under investigation but also against tau pathology. Results from amyloid-based immunotherapy studies in clinical trials indicate that intervention appears to be more effective in early stages of amyloid accumulation in particular solanezumab with a potential impact at mild Alzheimer's disease, highlighting the importance of diagnosing Alzheimer's disease as early as possible and undertaking clinical trials at this stage. In both phase III solanezumab and bapineuzumab trials, PET imaging revealed that about a quarter of patients lacked fibrillar amyloid pathology at baseline, suggesting that they did not have Alzheimer's disease in the first place. So a new third phase 3 clinical trial for solanezumab, called Expedition 3, in patients with mild Alzheimer's disease and evidence of amyloid burden has been started. Thus, currently, amyloid intervention is realized at early stage of the Alzheimer's disease in clinical trials, at prodromal Alzheimer's disease, or at asymptomatic subjects or at risk to develop Alzheimer's disease and or at asymptomatic subjects with autosomal dominant mutation. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  12. How Alzheimer's Changes the Brain

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    Full Text Available ... has been rented. This feature is not available right now. Please try again later. Published on Aug 23, 2017 This 4-minute video shows how Alzheimer’s affects the human brain and looks at promising ideas to treat ...

  13. Neuroimaging Measures as Endophenotypes in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Meredith N. Braskie

    2011-01-01

    Full Text Available Late onset Alzheimer's disease (AD is moderately to highly heritable. Apolipoprotein E allele ε4 (APOE4 has been replicated consistently as an AD risk factor over many studies, and recently confirmed variants in other genes such as CLU, CR1, and PICALM each increase the lifetime risk of AD. However, much of the heritability of AD remains unexplained. AD is a complex disease that is diagnosed largely through neuropsychological testing, though neuroimaging measures may be more sensitive for detecting the incipient disease stages. Difficulties in early diagnosis and variable environmental contributions to the disease can obscure genetic relationships in traditional case-control genetic studies. Neuroimaging measures may be used as endophenotypes for AD, offering a reliable, objective tool to search for possible genetic risk factors. Imaging measures might also clarify the specific mechanisms by which proposed risk factors influence the brain.

  14. Calcium Hypothesis of Alzheimer's disease and brain aging: A framework for integrating new evidence into a comprehensive theory of pathogenesis.

    Science.gov (United States)

    2017-02-01

    This article updates the Calcium Hypothesis of Alzheimer's disease and brain aging on the basis of emerging evidence since 1994 (The present article, with the subtitle "New evidence for a central role of Ca 2+ in neurodegeneration," includes three appendices that provide context and further explanations for the rationale for the revisions in the updated hypothesis-the three appendices are as follows: Appendix I "Emerging concepts on potential pathogenic roles of [Ca 2+ ]," Appendix II "Future studies to validate the central role of dysregulated [Ca 2+ ] in neurodegeneration," and Appendix III "Epilogue: towards a comprehensive hypothesis.") (Marx J. Fresh evidence points to an old suspect: calcium. Science 2007; 318:384-385). The aim is not only to re-evaluate the original key claims of the hypothesis with a critical eye but also to identify gaps in knowledge required to validate relevant claims and delineate additional studies and/or data that are needed. Some of the key challenges for this effort included examination of questions regarding (1) the temporal and spatial relationships of molecular mechanisms that regulate neuronal calcium ion (Ca 2+ ), (2) the role of changes in concentration of calcium ion [Ca 2+ ] in various subcellular compartments of neurons, (3) how alterations in Ca 2+ signaling affect the performance of neurons under various conditions, ranging from optimal functioning in a healthy state to conditions of decline and deterioration in performance during aging and in disease, and (4) new ideas about the contributions of aging, genetic, and environmental factors to the causal relationships between dysregulation of [Ca 2+ ] and the functioning of neurons (see Appendices I and II). The updated Calcium Hypothesis also includes revised postulates that are intended to promote further crucial experiments to confirm or reject the various predictions of the hypothesis (see Appendix III). Copyright © 2016 the Alzheimer's Association. All rights reserved.

  15. Complexation as an approach to entrap cationic drugs into cationic nanoparticles administered intranasally for Alzheimer's disease management: preparation and detection in rat brain.

    Science.gov (United States)

    Hanafy, Amira S; Farid, Ragwa M; ElGamal, Safaa S

    2015-01-01

    Complexation was investigated as an approach to enhance the entrapment of the cationic neurotherapeutic drug, galantamine hydrobromide (GH) into cationic chitosan nanoparticles (CS-NPs) for Alzheimer's disease management intranasally. Biodegradable CS-NPs were selected due to their low production cost and simple preparation. The effects of complexation on CS-NPs physicochemical properties and uptake in rat brain were examined. Placebo CS-NPs were prepared by ionic gelation, and the parameters affecting their physicochemical properties were screened. The complex formed between GH and chitosan was detected by the FT-IR study. GH/chitosan complex nanoparticles (GH-CX-NPs) were prepared by ionic gelation, and characterized in terms of particle size, zeta potential, entrapment efficiency, in vitro release and stability for 4 and 25 °C for 3 months. Both placebo CS-NPs and GH-CX-NPs were visualized by transmission electron microscopy. Rhodamine-labeled GH-CX-NPs were prepared, administered to male Wistar rats intranasally, and their delivery to different brain regions was detected 1 h after administration using fluorescence microscopy and software-aided image processing. Optimized placebo CS-NPs and GH-CX-NPs had a diameter 182 and 190 nm, and a zeta potential of +40.4 and +31.6 mV, respectively. GH encapsulation efficiency and loading capacity were 23.34 and 9.86%, respectively. GH/chitosan complexation prolonged GH release (58.07% ± 6.67 after 72 h), improved formulation stability at 4 °C in terms of drug leakage and particle size, and showed insignificant effects on the physicochemical properties of the optimized placebo CS-NPs (p > 0.05). Rhodamine-labeled GH-CX-NPs were detected in the olfactory bulb, hippocampus, orbitofrontal and parietal cortices. Complexation is a promising approach to enhance the entrapment of cationic GH into the CS-NPs. It has insignificant effect on the physicochemical properties of CS-NPs. GH-CX-NPs were successfully

  16. Amyloid-β Derived from the Brain of the Alzheimer's Disease Transgenic Mouse Is Resistant to Proteolytic Digestion Due to Its Conformation.

    Science.gov (United States)

    Chen, Baian; Zhang, Jing; Wang, Shubo; Wang, Wen; Yao, Zitong; Sun, Quan; Wu, Yi; Lu, Jing

    2017-08-01

    The main pathological feature of Alzheimer's disease (AD) is the formation of abundant amyloid-β (Aβ) plaques in the human brain. Studies have reported that Aβ from the AD brain is resistant to proteolytic digestion, which may explain why Aβ cannot be readily eliminated from this organ. However, there are only a few studies that address this important question. We used the AD transgenic mouse (APP/PS1) model to show that Aβ derived from the brain of the old mouse is resistant to proteolytic digestion. This was in contrast to the proteinase K-sensitive human Aβ peptide, whose amino acid sequence was identical to that of AD mouse-derived Aβ but whose conformation was different (i.e., the native protein, but not the peptide, folded into a three-dimensional conformation). To address this question, we denatured AD mouse-derived Aβ with urea and found that Aβ became proteinase K-sensitive. This phenomenon was concentration-dependent, and these results were confirmed by another protein denaturant, guanidinium hydrochloride. We recovered the conformation of the denatured AD mouse-derived Aβ by eliminating urea and adding the human Aβ peptide, and we found that human Aβ was converted to the proteinase K-resistant form in the presence of partially undenatured AD mouse-derived Aβ. However, upon the addition of the rat Aβ peptide, there were no Aβ proteinase K-resistant fragments. Our results show that the resistance of AD mouse-derived Aβ to proteolytic digestion is dependent on the three-dimensional conformation of Aβ. In summary, this study provides new insights on why Aβ plaques fail to be degraded in the human brain.

  17. Detection of subjects and brain regions related to Alzheimer's disease using 3D MRI scans based on eigenbrain and machine learning.

    Science.gov (United States)

    Zhang, Yudong; Dong, Zhengchao; Phillips, Preetha; Wang, Shuihua; Ji, Genlin; Yang, Jiquan; Yuan, Ti-Fei

    2015-01-01

    Early diagnosis or detection of Alzheimer's disease (AD) from the normal elder control (NC) is very important. However, the computer-aided diagnosis (CAD) was not widely used, and the classification performance did not reach the standard of practical use. We proposed a novel CAD system for MR brain images based on eigenbrains and machine learning with two goals: accurate detection of both AD subjects and AD-related brain regions. First, we used maximum inter-class variance (ICV) to select key slices from 3D volumetric data. Second, we generated an eigenbrain set for each subject. Third, the most important eigenbrain (MIE) was obtained by Welch's t-test (WTT). Finally, kernel support-vector-machines with different kernels that were trained by particle swarm optimization, were used to make an accurate prediction of AD subjects. Coefficients of MIE with values higher than 0.98 quantile were highlighted to obtain the discriminant regions that distinguish AD from NC. The experiments showed that the proposed method can predict AD subjects with a competitive performance with existing methods, especially the accuracy of the polynomial kernel (92.36 ± 0.94) was better than the linear kernel of 91.47 ± 1.02 and the radial basis function (RBF) kernel of 86.71 ± 1.93. The proposed eigenbrain-based CAD system detected 30 AD-related brain regions (Anterior Cingulate, Caudate Nucleus, Cerebellum, Cingulate Gyrus, Claustrum, Inferior Frontal Gyrus, Inferior Parietal Lobule, Insula, Lateral Ventricle, Lentiform Nucleus, Lingual Gyrus, Medial Frontal Gyrus, Middle Frontal Gyrus, Middle Occipital Gyrus, Middle Temporal Gyrus, Paracentral Lobule, Parahippocampal Gyrus, Postcentral Gyrus, Posterial Cingulate, Precentral Gyrus, Precuneus, Subcallosal Gyrus, Sub-Gyral, Superior Frontal Gyrus, Superior Parietal Lobule, Superior Temporal Gyrus, Supramarginal Gyrus, Thalamus, Transverse Temporal Gyrus, and Uncus). The results were coherent with existing literatures. The eigenbrain method

  18. Expression of tryptophan 2,3-dioxygenase and production of kynurenine pathway metabolites in triple transgenic mice and human Alzheimer's disease brain.

    Directory of Open Access Journals (Sweden)

    Wei Wu

    Full Text Available To assess the role of the kynurenine pathway in the pathology of Alzheimer's disease (AD, the expression and localization of key components of the kynurenine pathway including the key regulatory enzyme tryptophan 2,3 dioxygenase (TDO, and the metabolites tryptophan, kynurenine, kynurenic acid, quinolinic acid and picolinic acid were assessed in different brain regions of triple transgenic AD mice. The expression and cell distribution of TDO and quinolinic acid, and their co-localization with neurofibrillary tangles and senile β amyloid deposition were also determined in hippocampal sections from human AD brains. The expression of TDO mRNA was significantly increased in the cerebellum of AD mouse brain. Immunohistochemistry demonstrated that the density of TDO immuno-positive cells was significantly higher in the AD mice. The production of the excitotoxin quinolinic acid strongly increased in the hippocampus in a progressive and age-dependent manner in AD mice. Significantly higher TDO and indoleamine 2,3 dioxygenase 1 immunoreactivity was observed in the hippocampus of AD patients. Furthermore, TDO co-localizes with quinolinic acid, neurofibrillary tangles-tau and amyloid deposits in the hippocampus of AD. These results show that the kynurenine pathway is over-activated in AD mice. This is the first report demonstrating that TDO is highly expressed in the brains of AD mice and in AD patients, suggesting that TDO-mediated activation of the kynurenine pathway could be involved in neurofibrillary tangles formation and associated with senile plaque. Our study adds to the evidence that the kynurenine pathway may play important roles in the neurodegenerative processes of AD.

  19. Inhibitory effect of some tropical green leafy vegetables on key enzymes linked to Alzheimer's disease and some pro-oxidant induced lipid peroxidation in rats' brain.

    Science.gov (United States)

    Oboh, Ganiyu; Akinyemi, Ayodele Jacobson; Ademiluyi, Adedayo Oluwaseun; Bello, Fatai Olumide

    2014-05-01

    This study sought to investigate the inhibitory effect of some commonly consumed Nigerian green leafy vegetables (raw and blanched) on acetylcholinesterase and butyrylcholinesterase (key enzyme linked to Alzheimer's disease) activities and some pro-oxidants (FeSO4, Sodium nitroprusside and Quinolinic acid) induced lipid peroxidation in rat brain in vitro. Three commonly consumed green leafy vegetables in Nigeria [Amarantus cruentus (Arowojeja), Struchium sparganophora (Ewuro-odo) and Telfairia occidentalis (Ugwu] were blanched in hot water for 10 min, and the extracts of the raw and blanched vegetables were prepared and used for subsequent analysis. The result revealed that all the vegetables inhibited acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity as well as the pro-oxidants induced lipid peroxidation in rat brain in a dose dependent manner; however, Amarantus cruentus extract (EC50 = 97.9 μg/ml) had the highest inhibitory effect on acetylcholinesterase activity while Telfairia occidentalis extract (EC50 = 52.7 μg/ml) had the highest inhibitory effect on butyrylcholinesterase activity. However, blanching of the vegetables caused a significant (P vegetables on AChE activities while it enhanced the inhibition of the pro-oxidants induced lipid peroxidation in rat brain in vitro. Therefore, some of the possible mechanism by which green leafy vegetables exert their neuroprotective activities could be through the inhibition of acetylcholinesterase and butyrylcholinesterase activities and prevention of lipid peroxidation in the brain. However, blanching of the vegetables could reduce their ability to inhibit acetylcholinesterase and butyrylcholinesterase activity.

  20. Towards an All-Polymer Biosensor for Early Alzheimer's Disease

    DEFF Research Database (Denmark)

    Christiansen, Nikolaj Ormstrup; Heegaard, Niels

    Alzheimer's disease (AD) is quickly evolving into one of the biggest and most costly health issues in Europe and the United States. AD is a protein misfolding disease, caused by accumulation of abnormally folded β-amyloid and tau protein in the brain. The build-up of protein is believed...... to degenerate the brain tissue literally shrinking the brain. This slowly destroys function of these parts of the brain. It has been discovered that the concentration of A42 in cerebrospinal fluid (CSF) is a biomarker for this disease. It is therefor of great interest to develop quick and low cost methods...

  1. The hydroxylated form of docosahexaenoic acid (DHA-H) modifies the brain lipid composition in a model of Alzheimer's disease, improving behavioral motor function and survival.

    Science.gov (United States)

    Mohaibes, Raheem J; Fiol-deRoque, María A; Torres, Manuel; Ordinas, Margarita; López, David J; Castro, José A; Escribá, Pablo V; Busquets, Xavier

    2017-09-01

    We have compared the effect of the commonly used ω-3 fatty acid, docosahexaenoic acid ethyl ester (DHA-EE), and of its 2-hydroxylated DHA form (DHA-H), on brain lipid composition, behavior and lifespan in a new human transgenic Drosophila melanogaster model of Alzheimer's disease (AD). The transgenic flies expressed human Aβ42 and tau, and the overexpression of these human transgenes in the CNS of these flies produced progressive defects in motor function (antigeotaxic behavior) while reducing the animal's lifespan. Here, we demonstrate that both DHA-EE and DHA-H increase the longer chain fatty acids (≥18C) species in the heads of the flies, although only DHA-H produced an unknown chromatographic peak that corresponded to a non-hydroxylated lipid. In addition, only treatment with DHA-H prevented the abnormal climbing behavior and enhanced the lifespan of these transgenic flies. These benefits of DHA-H were confirmed in the well characterized transgenic PS1/APP mouse model of familial AD (5xFAD mice), mice that develop defects in spatial learning and in memory, as well as behavioral deficits. Hence, it appears that the modulation of brain lipid composition by DHA-H could have remedial effects on AD associated neurodegeneration. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá. Copyright © 2017. Published by Elsevier B.V.

  2. Antroquinonol Lowers Brain Amyloid-β Levels and Improves Spatial Learning and Memory in a Transgenic Mouse Model of Alzheimer's Disease.

    Science.gov (United States)

    Chang, Wen-Han; Chen, Miles C; Cheng, Irene H

    2015-10-15

    Alzheimer's disease (AD) is the most common form of dementia. The deposition of brain amyloid-β peptides (Aβ), which are cleaved from amyloid precursor protein (APP), is one of the pathological hallmarks of AD. Aβ-induced oxidative stress and neuroinflammation play important roles in the pathogenesis of AD. Antroquinonol, a ubiquinone derivative isolated from Antrodia camphorata, has been shown to reduce oxidative stress and inflammatory cytokines via activating the nuclear transcription factor erythroid-2-related factor 2 (Nrf2) pathway, which is downregulated in AD. Therefore, we examined whether antroquinonol could improve AD-like pathological and behavioral deficits in the APP transgenic mouse model. We found that antroquinonol was able to cross the blood-brain barrier and had no adverse effects via oral intake. Two months of antroquinonol consumption improved learning and memory in the Morris water maze test, reduced hippocampal Aβ levels, and reduced the degree of astrogliosis. These effects may be mediated through the increase of Nrf2 and the decrease of histone deacetylase 2 (HDAC2) levels. These findings suggest that antroquinonol could have beneficial effects on AD-like deficits in APP transgenic mouse.

  3. Voxel-wise co-analysis of macro- and microstructural brain alteration in mild cognitive impairment and Alzheimer's disease using anatomical and diffusion MRI.

    Science.gov (United States)

    Cardenas, Valerie A; Tosun, Duygu; Chao, Linda L; Fletcher, P Thomas; Joshi, Sarang; Weiner, Michael W; Schuff, Norbert

    2014-01-01

    To determine if a voxel-wise "co-analysis" of structural and diffusion tensor magnetic resonance imaging (MRI) together reveals additional brain regions affected in mild cognitive impairment (MCI) and Alzheimer's disease (AD) than voxel-wise analysis of the individual MRI modalities alone. Twenty-one patients with MCI, 21 patients with AD, and 21 cognitively normal healthy elderly were studied with MRI. Maps of deformation and fractional anisotropy (FA) were computed and used as dependent variables in univariate and multivariate statistical models. Univariate voxel-wise analysis of macrostructural changes in MCI showed atrophy in the right anterior temporal lobe, left posterior parietal/precuneus region, WM adjacent to the cingulate gyrus, and dorsolateral prefrontal regions, consistent with prior research. Univariate voxel-wise analysis of microstructural changes in MCI showed reduced FA in the left posterior parietal region extending into the corpus callosum, consistent with previous work. The multivariate analysis, which provides more information than univariate tests when structural and FA measures are correlated, revealed additional MCI-related changes in corpus callosum and temporal lobe. These results suggest that in corpus callosum and temporal regions macro- and microstructural variations in MCI can be congruent, providing potentially new insight into the mechanisms of brain tissue degeneration. Copyright © 2013 by the American Society of Neuroimaging.

  4. Secreted and Transmembrane αKlotho Isoforms Have Different Spatio-Temporal Profiles in the Brain during Aging and Alzheimer's Disease Progression.

    Directory of Open Access Journals (Sweden)

    Anna Massó

    Full Text Available The Klotho protein is a β-glucuronidase, and its overexpression is associated with life extension. Its mechanism of action is not fully understood, although it has been recently reported that αKlotho improves synaptic and cognitive functions, and it may also influence a variety of structures and functions during CNS maturation and aging. The αKlotho gene has two transcripts, one encoding a transmembrane isoform (m-KL, and the other a putative secreted isoform (s-KL. Unfortunately, little is known about the secreted αKlotho isoform, since available antibodies cannot discriminate s-KL from the KL1 domain cleaved from the transmembrane isoform. This study shows, for the first time, that the klotho transcript produced by alternative splicing generates a stable protein (70 kDa, and that in contrast to the transmembrane Klotho isoform, it is ten times more abundant in the brain than in the kidney suggesting that the two isoforms may have different functions. We also studied whether klotho expression in the CNS was influenced by aging, Alzheimer's disease (AD, or a healthy lifestyle, such as voluntary moderate continuous exercise. We observed a strong correlation between high expression levels of the two klotho transcripts and the healthy status of the animals. Expression of Klotho in brain areas decayed more rapidly in the 3xTg-AD model of AD than in healthy animals, whilst moderate continuous exercise in adulthood prevents the decline in expression of both klotho transcripts.

  5. Secreted and Transmembrane αKlotho Isoforms Have Different Spatio-Temporal Profiles in the Brain during Aging and Alzheimer's Disease Progression

    Science.gov (United States)

    Massó, Anna; Sánchez, Angela; Gimenez-Llort, Lydia; Lizcano, Jose Miguel; Cañete, Manuel; García, Belen; Torres-Lista, Virginia; Puig, Meritxell; Bosch, Assumpció; Chillon, Miguel

    2015-01-01

    The Klotho protein is a β-glucuronidase, and its overexpression is associated with life extension. Its mechanism of action is not fully understood, although it has been recently reported that αKlotho improves synaptic and cognitive functions, and it may also influence a variety of structures and functions during CNS maturation and aging. The αKlotho gene has two transcripts, one encoding a transmembrane isoform (m-KL), and the other a putative secreted isoform (s-KL). Unfortunately, little is known about the secreted αKlotho isoform, since available antibodies cannot discriminate s-KL from the KL1 domain cleaved from the transmembrane isoform. This study shows, for the first time, that the klotho transcript produced by alternative splicing generates a stable protein (70 kDa), and that in contrast to the transmembrane Klotho isoform, it is ten times more abundant in the brain than in the kidney suggesting that the two isoforms may have different functions. We also studied whether klotho expression in the CNS was influenced by aging, Alzheimer's disease (AD), or a healthy lifestyle, such as voluntary moderate continuous exercise. We observed a strong correlation between high expression levels of the two klotho transcripts and the healthy status of the animals. Expression of Klotho in brain areas decayed more rapidly in the 3xTg-AD model of AD than in healthy animals, whilst moderate continuous exercise in adulthood prevents the decline in expression of both klotho transcripts. PMID:26599613

  6. Costs of Alzheimer's disease (in Dutch); A study of the most important cost items of patients with Alzheimer's disease in the Netherlands and in France

    NARCIS (Netherlands)

    N. van der Roer; J.J. van Busschbach (Jan); E.S. Goes; L. van Hakkaart-van Roijen (Leona)

    2001-01-01

    textabstractThe most frequently occurring type of dementia is Alzheimer's disease. Alzheimer's disease is a degenerative illness affecting the brain, decreasing the patient's memory and judgement. A cure is not available but it is possible to delay the cognitive decline with medication. New drugs

  7. Effect and mechanism of acupuncture on Alzheimer's disease.

    Science.gov (United States)

    Zeng, Bai-Yun; Salvage, Sarah; Jenner, Peter

    2013-01-01

    Alzheimer's disease is the most common form of dementia diagnosed in the aging population worldwide. The cause of Alzheimer's is still not clear. There is no cure for the disease and current treatments are only symptomatic relieve. The search for new treatment is made ever more urgent due to increasing population aging. Acupuncture has been in practice in China for more than 3000 years and used to treat a wide variety of conditions including cardiovascular and psychiatric diseases, acute, and chronic pain. In this chapter, we review recent development on the effects and mechanisms of acupuncture on Alzheimer's disease. In Alzheimer's animal models, acupuncture stimulation at acupoints enhances cholinergic neurotransmission, trophic factor releasing, reduces apoptotic and oxidative damages, improves synaptic plasticity and decreases the levels of Aβ proteins in the hippocampus and relevant brain regions. The biochemical modulations by acupuncture in the brains of Alzheimer's models are correlated with the cognitive improvement. In Alzheimer's patients, functional brain images demonstrated that acupuncture increased in the activity in the temporal lobe and prefrontal lobe which are related to the memory and cognitive function. Although only a few acupuncture clinical studies with a small number of participants are reported, they represent an important step forward in the research of both acupuncture and Alzheimer's. Translation of acupuncture research in animal model studies into the human subjects will undoubtedly enhance acupuncture efficacy in clinical study and treatment which could eventually lead to a safer, well-tolerated and inexpensive form of care for Alzheimer's patients. © 2013 Elsevier Inc. All rights reserved.

  8. Alzheimer's disease: new diagnostic and therapeutic tools

    Directory of Open Access Journals (Sweden)

    Caruso Calogero

    2008-08-01

    Full Text Available Abstract On March 19, 2008 a Symposium on Pathophysiology of Ageing and Age-Related diseases was held in Palermo, Italy. Here, the lectures of M. Racchi on History and future perspectives of Alzheimer Biomarkers and of G. Scapagnini on Cellular Stress Response and Brain Ageing are summarized. Alzheimer's disease (AD is a heterogeneous and progressive neurodegenerative disease, which in Western society mainly accounts for clinica dementia. AD prevention is an important goal of ongoing research. Two objectives must be accomplished to make prevention feasible: i individuals at high risk of AD need to be identified before the earliest symptoms become evident, by which time extensive neurodegeneration has already occurred and intervention to prevent the disease is likely to be less successful and ii safe and effective interventions need to be developed that lead to a decrease in expression of this pathology. On the whole, data here reviewed strongly suggest that the measurement of conformationally altered p53 in blood cells has a high ability to discriminate AD cases from normal ageing, Parkinson's disease and other dementias. On the other hand, available data on the involvement of curcumin in restoring cellular homeostasis and rebalancing redox equilibrium, suggest that curcumin might be a useful adjunct in the treatment of neurodegenerative illnesses characterized by inflammation, such as AD.

  9. Time to Amyloid Positivity and Preclinical Changes in Brain Metabolism, Atrophy, and Cognition: Evidence for Emerging Amyloid Pathology in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Philip S. Insel

    2017-05-01

    Full Text Available Background: Aβ pathology is associated with longitudinal changes of brain metabolism, atrophy, and cognition, in cognitively healthy elders. However, Aβ information is usually measured cross-sectionally and dichotomized to classify subjects as Aβ-positive or Aβ-negative, making it difficult to evaluate when brain and cognitive changes occur with respect to emerging Aβ pathology. In this study, we use longitudinal Aβ information to combine the level and rate of change of Aβ to estimate the time to Aβ-positivity for each subject and test this temporal proximity to significant Aβ pathology for associations with brain structure, metabolism, and cognition.Methods: In 89 cognitively healthy elders with up to 10 years of follow-up, we estimated the points at which rates of fluorodeoxyglucose (FDG PET, MRI, and cognitive and functional decline begin to accelerate with respect to the time to Aβ-positivity. Points of initial acceleration in rates of decline were estimated using mixed-effects models with penalized regression splines.Results: Acceleration of rates of FDG PET were observed to occur 20+ years before the conventional threshold for Aβ-positivity. Subtle signs of cognitive dysfunction were observed 10+ years before Aβ-positivity.Conclusions: Aβ may have subtle associations with other hallmarks of Alzheimer's disease before Aβ biomarkers reach conventional thresholds for Aβ-positivity. Therefore, we propose that emerging Aβ pathology occurs many years before cognitively healthy elders reach the current threshold for Aβ positivity (preclinical AD. To allow prevention in the earliest disease stages, AD clinical trials may be designed to also include subjects with Aβ biomarkers in the sub-threshold range.

  10. Mathematical model on Alzheimer's disease.

    Science.gov (United States)

    Hao, Wenrui; Friedman, Avner

    2016-11-18

    Alzheimer disease (AD) is a progressive neurodegenerative disease that destroys memory and cognitive skills. AD is characterized by the presence of two types of neuropathological hallmarks: extracellular plaques consisting of amyloid β-peptides and intracellular neurofibrillary tangles of hyperphosphorylated tau proteins. The disease affects 5 million people in the United States and 44 million world-wide. Currently there is no drug that can cure, stop or even slow the progression of the disease. If no cure is found, by 2050 the number of alzheimer's patients in the U.S. will reach 15 million and the cost of caring for them will exceed $ 1 trillion annually. The present paper develops a mathematical model of AD that includes neurons, astrocytes, microglias and peripheral macrophages, as well as amyloid β aggregation and hyperphosphorylated tau proteins. The model is represented by a system of partial differential equations. The model is used to simulate the effect of drugs that either failed in clinical trials, or are currently in clinical trials. Based on these simulations it is suggested that combined therapy with TNF- α inhibitor and anti amyloid β could yield significant efficacy in slowing the progression of AD.

  11. The Role of Insulin, Insulin Growth Factor, and Insulin-Degrading Enzyme in Brain Aging and Alzheimer's Disease

    OpenAIRE

    Messier, Claude; Teutenberg, Kevin

    2005-01-01

    Most brain insulin comes from the pancreas and is taken up by the brain by what appears to be a receptor-based carrier. Type 2 diabetes animal models associated with insulin resistance show reduced insulin brain uptake and content. Recent data point to changes in the insulin receptor cascade in obesity-related insulin resistance, suggesting that brain insulin receptors also become less sensitive to insulin, which could reduce synaptic plasticity. Insulin transport to the brain is reduced in a...

  12. Alzheimer's disease prevention: A way forward.

    Science.gov (United States)

    Bermejo-Pareja, F; Llamas-Velasco, S; Villarejo-Galende, A

    2016-12-01

    This review proposes a more optimistic view of Alzheimer's disease (AD), in contrast to that contributed by the ageing of the population and the failure of potentially curative therapies (vaccines and others). Treatment failure is likely due to the fact that AD gestates in the brain for decades but manifests in old age. This review updates the concept of AD and presents the results of recent studies that show that primary prevention can reduce the incidence and delay the onset of the disease. Half of all cases of AD are potentially preventable through education, the control of cardiovascular risk factors, the promotion of healthy lifestyles and specific drug treatments. These approaches could substantially reduce the future incidence rate of this disease. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  13. Alzheimer's Disease and Exercise: A Literature Review.

    Science.gov (United States)

    Cass, Shane P

    Alzheimer's disease (AD) is a progressive neurodegenerative disease that impairs memory and cognitive judgment. It is the leading cause of dementia in late adult life and is associated with a significant social burden and increased morbidity and mortality in the elderly. Because of mixed effectiveness of medications, exercise has been considered as a treatment for pre-clinical AD, late stage AD, and as a prevention strategy. Exercise appears to improve brain blood flow, increase hippocampal volume, and improve neurogenesis. Prospective studies indicate that physical inactivity is one of the most common preventable risk factors for developing AD and that higher physical activity levels are associated with a reduced risk of development of disease. Exercise as a treatment for AD shows improvement in cognitive function, decreased neuropsychiatric symptoms, and a slower decline in activities of daily living (ADL). Exercise has been shown to have fewer side effects and better adherence compared to medications.

  14. Fish oil feeding attenuates neuroinflammatory gene expression without concomitant changes in brain eicosanoids and docosanoids in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Hopperton, Kathryn E; Trépanier, Marc-Olivier; James, Nicholas C E; Chouinard-Watkins, Raphaël; Bazinet, Richard P

    2018-03-01

    Neuroinflammation is a recognized hallmark of Alzheimer's disease, along with accumulation of amyloid-β plaques, neurofibrillary tangles and synaptic loss. n-3 polyunsaturated fatty acids (PUFA) and molecules derived from them, including eicosapentaenoic acid-derived eicosanoids and docosahexaenoic acid-derived docosanoids, are known to have both anti-inflammatory and pro-resolving properties, while human observational data links consumption of these fatty acids to a decreased risk of Alzheimer's disease. Few studies have examined the neuroinflammation-modulating effects of n-3 PUFA feeding in an Alzheimer's disease-related model, and none have investigated whether these effects are mediated by changes in brain eicosanoids and docosanoids. Here, we use both a fat-1 transgenic mouse and a fish oil feeding model to study the impact of increasing tissue n-3 PUFA on neuroinflammation and the production of pro-inflammatory and pro-resolving lipid mediators. Fat-1 mice, transgenic animals that can convert n-6 to n-3 PUFA, and their wildtype littermates were fed diets containing either fish oil (high n-3 PUFA) or safflower oil (negligible n-3 PUFA) from weaning to 12 weeks. Animals then underwent intracerebroventricular infusion of either amyloid-β 1-40 or a control peptide. Hippocampi were collected from non-surgery and surgery animals 10 days after infusion. Microarray was used to measure enrichment of inflammation-associated gene categories and expression of genes involved in the synthesis of lipid mediators. Results were validated by real-time PCR in a separate cohort of animals. Lipid mediators were measured via liquid chromatography tandem mass spectrometry. Fat-1 and wildtype mice fed fish oil had higher total hippocampal DHA than wildtype mice fed the safflower oil diet. The safflower-fed mice, but not the fat-1 or fish oil-fed mice, had significantly increased expression in gene ontology categories associated with inflammation in response to amyloid

  15. Understanding Alzheimer's

    Science.gov (United States)

    ... Navigation Bar Home Current Issue Past Issues Understanding Alzheimer's Past Issues / Fall 2007 Table of Contents For ... and brain scans. No treatment so far stops Alzheimer's. However, for some in the disease's early and ...

  16. Analysis of Regional Cerebral Blood Flow Using 99mTc-HMPAO Brain SPECT in Senile Dementia of Alzheimer Type

    International Nuclear Information System (INIS)

    Lee, Myung Hae; Lee, Myung Chul; Koh, Chang Soon; Roh, Jae Kyu; Woo, Chong In

    1988-01-01

    99m Tc-HMPAO brain SPECT studies were performed in 11 patients with Alzheimer's disease, 7 patients with psychological depression and 12 normal controls. Changes of regional cerebral blood flow was semiquantitatively analyzed and the results were as follows. 1) In 11 patients with Alzheimer's disease, significant reduction of regional cerebral blood flow was found In both temporoparietal areas. 2) Relative perfusion between cerebral hemispheres was rather symmetrical in patient with Alzheimer's disease. 3) All patients with depression showed normal SPECT findings. As for conclusion, 99m Tc-HMPAO brain SPECT seemed to be a valuable method for clinical assessment and management of patients with Alzheimer's disease.

  17. Nasal steroids as a possible treatment for Alzheimer's disease.

    Science.gov (United States)

    Lehrer, Steven; Rheinstein, Peter H

    2017-10-01

    Quite a number of experimental treatments, which are based on conventionally accepted understandings of Alzheimer's disease, have not yielded expected results. Therefore, conventionally accepted understanding of the mechanisms of the disease may be inadequate or even wrong. The characteristic amyloid plaques and tau tangles in the brain may be a result, not a cause. Alzheimer's disease is more likely the product of neuroinflammation and deranged brain wound healing. If so, a hypothesized treatment, intranasal glucocorticoids, might be effective. Long-term use of intranasal glucocorticoids (especially older generation steroids) for Alzheimer's treatment would potentially raise intraocular pressure, but newer intranasal steroids (fluticasone, triamcinolone, or budesonide) have a minimal effect on intraocular pressure because of their low bioavailability.

  18. Caregiving for Alzheimer's Disease or Other Dementia

    Science.gov (United States)

    ... What's this? Submit Button Caregiving for Person with Alzheimer's Disease or a related Dementia Recommend on Facebook Tweet Share Compartir What is Alzheimer’s Disease? Alzheimer’s disease is the most common form ...

  19. Eye movements in Alzheimer's disease.

    Science.gov (United States)

    Molitor, Robert J; Ko, Philip C; Ally, Brandon A

    2015-01-01

    A growing body of literature has investigated changes in eye movements as a result of Alzheimer's disease (AD). When compared to healthy, age-matched controls, patients display a number of remarkable alterations to oculomotor function and viewing behavior. In this article, we review AD-related changes to fundamental eye movements, such as saccades and smooth pursuit motion, in addition to changes to eye movement patterns during more complex tasks like visual search and scene exploration. We discuss the cognitive mechanisms that underlie these changes and consider the clinical significance of eye movement behavior, with a focus on eye movements in mild cognitive impairment. We conclude with directions for future research.

  20. The fitness for the Ageing Brain Study II (FABS II: protocol for a randomized controlled clinical trial evaluating the effect of physical activity on cognitive function in patients with Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Ames David

    2010-12-01

    Full Text Available Abstract Background Observational studies have documented a potential protective effect of physical exercise in older adults who are at risk for developing Alzheimer's disease. The Fitness for the Ageing Brain II (FABS II study is a multicentre randomized controlled clinical trial (RCT aiming to determine whether physical activity reduces the rate of cognitive decline among individuals with Alzheimer's disease. This paper describes the background, objectives of the study, and an overview of the protocol including design, organization and data collection methods. Methods/Design The study will recruit 230 community-dwelling participants diagnosed with Alzheimer's disease. Participants will be randomly allocated to two treatment groups: usual care group or 24-week home-based program consisting of 150 minutes per week of tailored moderate physical activity. The primary outcome measure of the study is cognitive decline as measured by the change from baseline in the total score on the Alzheimer's disease Assessment Scale-Cognitive section. Secondary outcomes of interest include behavioral and psychological symptoms, quality of life, functional level, carer burden and physical function (strength, balance, endurance, physical activity. Primary endpoints will be measured at six and twelve months following the baseline assessment. Discussion This RCT will contribute evidence regarding the potential benefits of a systematic program of physical activity as an affordable and safe intervention for people with Alzheimer's disease. Further, if successful, physical activity in combination with usual care has the potential to alleviate the symptoms of Alzheimer's disease and improve its management and the quality of life of patients and their carers. Trial Registration Australia New Zealand Clinical Trials Registry ACTRN12609000755235

  1. Neuronal histamine and cognitive symptoms in Alzheimer's disease.

    Science.gov (United States)

    Zlomuzica, Armin; Dere, Dorothea; Binder, Sonja; De Souza Silva, Maria Angelica; Huston, Joseph P; Dere, Ekrem

    2016-07-01

    Alzheimer's disease is a neurodegenerative disorder characterized by extracellular amyloid plaque deposits, mainly composed of amyloid-beta peptide and intracellular neurofibrillary tangles consisting of aggregated hyperphosphorylated tau protein. Amyloid-beta represents a neurotoxic proteolytic cleavage product of amyloid precursor protein. The progressive cognitive decline that is associated with Alzheimer's disease has been mainly attributed to a deficit in cholinergic neurotransmission due to the continuous degeneration of cholinergic neurons e.g. in the basal forebrain. There is evidence suggesting that other neurotransmitter systems including neuronal histamine also contribute to the development and maintenance of Alzheimer's disease-related cognitive deficits. Pathological changes in the neuronal histaminergic system of such patients are highly predictive of ensuing cognitive deficits. Furthermore, histamine-related drugs, including histamine 3 receptor antagonists, have been demonstrated to alleviate cognitive symptoms in Alzheimer's disease. This review summarizes findings from animal and clinical research on the relationship between the neuronal histaminergic system and cognitive deterioration in Alzheimer's disease. The significance of the neuronal histaminergic system as a promising target for the development of more effective drugs for the treatment of cognitive symptoms is discussed. Furthermore, the option to use histamine-related agents as neurogenesis-stimulating therapy that counteracts progressive brain atrophy in Alzheimer's disease is considered. This article is part of a Special Issue entitled 'Histamine Receptors'. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. A new molecular model for Congo Red-β amyloid interaction: implications for diagnosis and inhibition of brain plaque formation in Alzheimer's disease

    Science.gov (United States)

    Zhang, Kristine A.; Li, Yat

    2015-08-01

    Alzheimer's disease (AD), an age-related neurodegenerative disorder, is the seventh leading cause of death in the United States. One strong pathological indicator of AD is senile plaques, which are aggregates of fibrils formed from amyloid β (Aβ) peptides. Thus, detection and inhibition of Aβ aggregation are critical for the prevention and treatment of AD. Congo red (CR) is one of the most widely used dye molecules for probing as well as inhabiting Aβ aggregation. However, the nature of interaction between CR and Aβ is not well understood. In this research, we systematically studied the interaction between CR and Aβ using a combination of optical techniques, including electronic absorption, fluorescence, Raman scattering, and circular dichroism, to provide detailed information with molecular specificity and high sensitivity. Compared to CR alone, interaction of the dye with Aβ results in a new absorption peak near 540 nm and significantly enhanced photoluminescence as well as Raman signal. Our results led us to propose a new model suggesting that CR exists primarily in a micellar form, resembling H-aggregates, in water and dissociates into monomers upon interaction with Aβ. This model has significant implications for the development of new strategies to detect and inhibit brain plaques for treatment of neurological diseases like AD.

  3. No change in total length of white matter fibers in Alzheimer's disease

    DEFF Research Database (Denmark)

    Jorgensen, A.M.; Marner, L.; Pakkenberg, B.

    2008-01-01

    White matter changes have been reported as part of Alzheimer dementia. To investigate this, the total subcortical myelinated nerve fiber length was estimated in postmortem brains from eight females (age 79-88 years) with severe Alzheimer's disease (AD) and compared with brains from 10 female...

  4. Cerebrospinal fluid lactate levels and brain [18F]FDG PET hypometabolism within the default mode network in Alzheimer's disease

    International Nuclear Information System (INIS)

    Liguori, Claudio; Chiaravalloti, Agostino; Schillaci, Orazio; Sancesario, Giuseppe; Stefani, Alessandro; Sancesario, Giulia Maria; Mercuri, Nicola Biagio; Pierantozzi, Mariangela

    2016-01-01

    It has been suggested that neuronal energy metabolism may be involved in Alzheimer's disease (AD). In this view, the finding of increased cerebrospinal fluid (CSF) lactate levels in AD patients has been considered the result of energetic metabolism dysfunction. Here, we investigated the relationship between neuronal energy metabolism, as measured via CSF lactate levels, and cerebral glucose metabolism, as stated at the 2-deoxy-2-(18F)fluoro-D-glucose positron emission tomography ([18F]FDG PET) in AD patients. AD patients underwent lumbar puncture to measure CSF lactate levels and [18F]FDG PET to assess brain glucose metabolism. CSF and PET data were compared to controls. Since patients were studied at rest, we specifically investigated brain areas active in rest-condition owing to the Default Mode Network (DMN). We correlated the CSF lactate concentrations with the [18F]FDG PET data in brain areas owing to the DMN, using sex, age, disease duration, Mini Mental State Examination, and CSF levels of tau proteins and beta-amyloid as covariates. AD patients (n = 32) showed a significant increase of CSF lactate levels compared to Control 1 group (n = 28). They also showed brain glucose hypometabolism in the DMN areas compared to Control 2 group (n = 30). Within the AD group we found the significant correlation between increased CSF lactate levels and glucose hypometabolism in Broadman areas (BA) owing to left medial prefrontal cortex (BA10, mPFC), left orbitofrontal cortex (BA11, OFC), and left parahippocampal gyrus (BA 35, PHG). We found high CSF levels of lactate and glucose hypometabolism within the DMN in AD patients. Moreover, we found a relationship linking the increased CSF lactate and the reduced glucose consumption in the left mPFC, OFC and PHG, owing to the anterior hub of DMN. These findings could suggest that neural glucose hypometabolism may affect the DMN efficiency in AD, also proposing the possible role of damaged brain energetic machine in impairing

  5. Cerebrospinal fluid lactate levels and brain [18F]FDG PET hypometabolism within the default mode network in Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Liguori, Claudio [University of Rome ' ' Tor Vergata' ' , Neurophysiopathology Unit, Department of Systems Medicine, Rome (Italy); University of Rome ' ' Tor Vergata' ' , Neurology Unit, Department of Systems Medicine, Rome (Italy); Chiaravalloti, Agostino; Schillaci, Orazio [University of Rome ' Tor Vergata' , Department of Biomedicine and Prevention, Rome (Italy); IRCSS Neuromed, Pozzilli (Italy); Sancesario, Giuseppe; Stefani, Alessandro [University of Rome ' ' Tor Vergata' ' , Neurology Unit, Department of Systems Medicine, Rome (Italy); IRCCS Fondazione Santa Lucia, Rome (Italy); Sancesario, Giulia Maria [IRCCS Fondazione Santa Lucia, Rome (Italy); Mercuri, Nicola Biagio [University of Rome ' ' Tor Vergata' ' , Neurophysiopathology Unit, Department of Systems Medicine, Rome (Italy); University of Rome ' ' Tor Vergata' ' , Neurology Unit, Department of Systems Medicine, Rome (Italy); IRCCS Fondazione Santa Lucia, Rome (Italy); Pierantozzi, Mariangela [University of Rome ' ' Tor Vergata' ' , Neurology Unit, Department of Systems Medicine, Rome (Italy)

    2016-10-15

    It has been suggested that neuronal energy metabolism may be involved in Alzheimer's disease (AD). In this view, the finding of increased cerebrospinal fluid (CSF) lactate levels in AD patients has been considered the result of energetic metabolism dysfunction. Here, we investigated the relationship between neuronal energy metabolism, as measured via CSF lactate levels, and cerebral glucose metabolism, as stated at the 2-deoxy-2-(18F)fluoro-D-glucose positron emission tomography ([18F]FDG PET) in AD patients. AD patients underwent lumbar puncture to measure CSF lactate levels and [18F]FDG PET to assess brain glucose metabolism. CSF and PET data were compared to controls. Since patients were studied at rest, we specifically investigated brain areas active in rest-condition owing to the Default Mode Network (DMN). We correlated the CSF lactate concentrations with the [18F]FDG PET data in brain areas owing to the DMN, using sex, age, disease duration, Mini Mental State Examination, and CSF levels of tau proteins and beta-amyloid as covariates. AD patients (n = 32) showed a significant increase of CSF lactate levels compared to Control 1 group (n = 28). They also showed brain glucose hypometabolism in the DMN areas compared to Control 2 group (n = 30). Within the AD group we found the significant correlation between increased CSF lactate levels and glucose hypometabolism in Broadman areas (BA) owing to left medial prefrontal cortex (BA10, mPFC), left orbitofrontal cortex (BA11, OFC), and left parahippocampal gyrus (BA 35, PHG). We found high CSF levels of lactate and glucose hypometabolism within the DMN in AD patients. Moreover, we found a relationship linking the increased CSF lactate and the reduced glucose consumption in the left mPFC, OFC and PHG, owing to the anterior hub of DMN. These findings could suggest that neural glucose hypometabolism may affect the DMN efficiency in AD, also proposing the possible role of damaged brain energetic machine in impairing

  6. The effect of focal brain injury on beta-amyloid plaque deposition, inflammation and synapses in the APP/PS1 mouse model of Alzheimer's disease.

    Science.gov (United States)

    Collins, Jessica M; King, Anna E; Woodhouse, Adele; Kirkcaldie, Matthew T K; Vickers, James C

    2015-05-01

    Traumatic brain injury is a risk factor for Alzheimer's disease (AD), however the effect of such neural damage on the onset and progression of beta-amyloid (Aβ) plaque pathology is not well understood. This study utilized an in vivo model of focal brain injury to examine how localized damage may acutely affect the onset and progression of Aβ plaque deposition as well as inflammatory and synaptic changes, in the APP/PS1 (APPSWE, PSEN1dE9) transgenic model of AD relative to wild-type (Wt) mice. Acute focal brain injury in 3- and 9-month-old APP/PS1 and Wt mice was induced by insertion of a needle into the somatosensory neocortex, as compared to sham surgery, and examined at 24h and 7d post-injury (PI). Focal brain injury did not induce thioflavine-S stained or (pan-Aβ antibody) MOAB-2-labeled plaques at either 24h or 7d PI in 3-month-old APP/PS1 mice or Wt mice. Nine-month-old APP/PS1 mice demonstrate cortical Aβ plaques but focal injury had no statistically significant (p>0.05) effect on thioflavine-S or MOAB-2 plaque load surrounding the injury site at 24h PI or 7d PI. There was a significant (p0.05). For both Wt and APP/PS1 mice alike, synaptophysin puncta near the injury site were significantly reduced 24h PI (compared to sites distant to the injury and the corresponding area in sham mice; p0.05). There was no significant effect of genotype on this response (p>0.05). These results indicate that focal brain injury and the associated microglial response do not acutely alter Aβ plaque deposition in the APP/PS1 mouse model. Furthermore the current study demonstrated that the brains of both Wt and APP/PS1 mice are capable of recovering lost synaptophysin immunoreactivity post-injury, the latter in the presence of Aβ plaque pathology that causes synaptic degeneration. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. How Alzheimer's Changes the Brain

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  8. How Alzheimer's Changes the Brain

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  9. How Alzheimer's Changes the Brain

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  10. How Alzheimer's Changes the Brain

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  11. How Alzheimer's Changes the Brain

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  12. How Alzheimer's Changes the Brain

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  13. How Alzheimer's Changes the Brain

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  14. How Alzheimer's Changes the Brain

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  15. Role of physical exercise in Alzheimer's disease.

    Science.gov (United States)

    Chen, Wei-Wei; Zhang, Xia; Huang, Wen-Juan

    2016-04-01

    The benefits of physical exercise on the brain and general wellness are well recognised, but not particularly well known to the general public. Understanding the importance of integrating active behavior for overall health is crucial at any age and particularly for the elderly who are at risk of developing Alzheimer's disease (AD), a disease mainly affecting individuals aged >65 years. AD is a neurodegenerative disease characterized by extracellular senile plaques of amyloid-β, intracellular neurofibrillary tangles of the protein tau, brain atrophy and dementia. The beneficial effects of physical exercise have been observed on the maintenance of brain size and efficiency for the prevention of AD risks, such as obesity, hypertension and stroke. These effects are extended to individuals with, or at risk of dementia and other age-related neurodegenerative disorders. Accordingly, although extensive studies are required to fully understand the mechanisms by which physical exercise procures beneficial effects, data suggest the relevance of integrating physical exercise in the prevention and/or cure of AD, disease whose incidence is predicted to increase in the future. Such an increase, may pose medical, social and economical challenges for populations and the health care system worldwide. In the present review we assess the positive aspects of physical exercise with regard to prevention and cure of AD.

  16. Role of physical exercise in Alzheimer's disease

    Science.gov (United States)

    CHEN, WEI-WEI; ZHANG, XIA; HUANG, WEN-JUAN

    2016-01-01

    The benefits of physical exercise on the brain and general wellness are well recognised, but not particularly well known to the general public. Understanding the importance of integrating active behavior for overall health is crucial at any age and particularly for the elderly who are at risk of developing Alzheimer's disease (AD), a disease mainly affecting individuals aged >65 years. AD is a neurodegenerative disease characterized by extracellular senile plaques of amyloid-β, intracellular neurofibrillary tangles of the protein tau, brain atrophy and dementia. The beneficial effects of physical exercise have been observed on the maintenance of brain size and efficiency for the prevention of AD risks, such as obesity, hypertension and stroke. These effects are extended to individuals with, or at risk of dementia and other age-related neurodegenerative disorders. Accordingly, although extensive studies are required to fully understand the mechanisms by which physical exercise procures beneficial effects, data suggest the relevance of integrating physical exercise in the prevention and/or cure of AD, disease whose incidence is predicted to increase in the future. Such an increase, may pose medical, social and economical challenges for populations and the health care system worldwide. In the present review we assess the positive aspects of physical exercise with regard to prevention and cure of AD. PMID:27073621

  17. Down-Regulation of Olfactory Receptors in Response to Traumatic Brain Injury Promotes Risk for Alzheimer’s Disease

    Science.gov (United States)

    2013-10-01

    fat diet aggravates the outcome of traumatic brain injury on hippocampal plasticity and cognitive function by reducing brain-derived neurotrophic...Oliva AA, Kang Y, Sanchez-Molano J, Furones C, Atkins CM (2012) STAT3 signaling after traumatic brain injury. J Neurochem 120, 710-720. [48] Chen T, Cao

  18. Solving the puzzle of Alzheimer disease.

    Science.gov (United States)

    Uriri-Glover, Johannah; McCarthy, Marianne; Cesarotti, Evelyn

    2012-09-10

    Managing patients with dementia and Alzheimer disease can be a challenge. Often, families and caregivers ask clinicians about the latest treatments. This article summarizes the latest evidence-based practice related to pharmacologic and nonpharmacologic management of patients with Alzheimer disease.

  19. Turning principles into practice in Alzheimer's disease

    NARCIS (Netherlands)

    Lindesay, J.; Bullock, R.; Daniels, H.; Emre, M.; Foerstl, H.; Froelich, L.; Gabryelewicz, T.; Martinez-Lage, P.; Monsch, A. U.; Tsolaki, M.; van Laar, T.

    P>The prevalence of dementia is reaching epidemic proportions globally, but there remain a number of issues that prevent people with dementia, their families and caregivers, from taking control of their condition. In 2008, Alzheimer's Disease International (ADI) launched a Global Alzheimer's Disease

  20. Amyloid imaging in prodromal Alzheimer's disease

    NARCIS (Netherlands)

    Ossenkoppele, R.; van Berckel, B.N.M.; Prins, N.D.

    2011-01-01

    Patients with mild cognitive impairment are at an increased risk of progression to Alzheimer's disease. However, not all patients with mild cognitive impairment progress, and it is difficult to accurately identify those patients who are in the prodromal stage of Alzheimer's disease. In a recent

  1. WITHDRAWN: Tacrine for Alzheimer's disease.

    Science.gov (United States)

    Qizilbash, N; Birks, J; Lopez Arrieta, J; Lewington, S; Szeto, S

    2007-07-18

    Tacrine is one of the first drugs to be widely marketed for the loss of memory and intellectual decline in Alzheimer's disease, often accompanied by abnormal behaviour and physical decline. The alleged success of tacrine in the treatment of these symptoms has been heralded as confirmation of the cholinergic theory of Alzheimer's disease. The efficacy of tacrine for symptoms of dementia remains controversial. This is reflected by the low rate of prescription of tacrine in countries where it is approved and the lack of approval by several regulatory authorities in Europe and elsewhere. The uncertainty about the efficacy of tacrine is due to the difficulties in interpretation of the results from the clinical trials. The reasons for this are the small effects of tacrine compared to placebo for all outcomes; the high incidence of adverse events; the lack of benefit observed in several trials; the use of cross-over designs and their associated methodological problems in a disease like dementia; the use of different measurement scales to assess outcome in different trials; and the problem of high dropout rates. To determine the clinical efficacy of tacrine for the symptoms of Alzheimer's disease. The Cochrane Dementia Group Register of Clinical Trials was searched using the terms 'tacrine', 'tetrahydroaminoacridine' and 'THA' (see the Group's search strategy for full details). All unconfounded, double-blind, randomized trials in which treatment with tacrine was administered for more than a day and compared to placebo in patients with dementia of the Alzheimer's type. Data were extracted independently by two reviewers, pooled if appropriate and possible, and the pooled odds ratios (95%CI) or the average differences (95%CI) were estimated. Where possible, intention-to-treat data were used. This review produced no clear results. The results were compatible with tacrine producing improvement, no change or even harm for those with Alzheimer's disease. It was not possible to

  2. Memantine Attenuates Alzheimer's Disease-Like Pathology and Cognitive Impairment.

    Directory of Open Access Journals (Sweden)

    Xiaochuan Wang

    Full Text Available Deficiency of protein phosphatase-2A is a key event in Alzheimer's disease. An endogenous inhibitor of protein phosphatase-2A, inhibitor-1, I1PP2A, which inhibits the phosphatase activity by interacting with its catalytic subunit protein phosphatase-2Ac, is known to be upregulated in Alzheimer's disease brain. In the present study, we overexpressed I1PP2A by intracerebroventricular injection with adeno-associated virus vector-1-I1PP2A in Wistar rats. The I1PP2A rats showed a decrease in brain protein phosphatase-2A activity, abnormal hyperphosphorylation of tau, neurodegeneration, an increase in the level of activated glycogen synthase kinase-3beta, enhanced expression of intraneuronal amyloid-beta and spatial reference memory deficit; littermates treated identically but with vector only, i.e., adeno-associated virus vector-1-enhanced GFP, served as a control. Treatment with memantine, a noncompetitive NMDA receptor antagonist which is an approved drug for treatment of Alzheimer's disease, rescued protein phosphatase-2A activity by decreasing its demethylation at Leu309 selectively and attenuated Alzheimer's disease-like pathology and cognitive impairment in adeno-associated virus vector-1-I1PP2A rats. These findings provide new clues into the possible mechanism of the beneficial therapeutic effect of memantine in Alzheimer's disease patients.

  3. Hierarchical clustering of Alzheimer and "normal" brains using elemental concentrations and glucose metabolism determined by PIXE, INAA and PET

    NARCIS (Netherlands)

    Cutts, DA; Spyrou, NM; Maguire, RP; Leenders, KL

    Brain tissue samples, obtained from the Alzheimer Disease Brain Bank, Institute of Psychiatry, London, were taken from both left and right hemispheres of three regions of the cerebrum, namely the frontal, parietal and occipital lobes for both Alzheimer and 'normal' subjects. Trace element

  4. Development of an UPLC-MS/MS method for simultaneous quantitation of 11 d-amino acids in different regions of rat brain: Application to a study on the associations of d-amino acid concentration changes and Alzheimer's disease.

    Science.gov (United States)

    Li, Zhe; Xing, Yuping; Guo, Xingjie; Cui, Yan

    2017-07-15

    There are significant differences in d-amino acid concentrations between healthy people and Alzheimer's disease patients. In order to investigate the potential correlation between d-amino acids and Alzheimer's disease, a simple and sensitive ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed. The method was applied to simultaneous determination of 11 d-amino acids in different regions of rat brain. Rat brain homogenates were firstly pretreated with protein precipitation procedure and then derivatized with (S)-N-(4-nitrophenoxycarbonyl) phenylalanine methoxyethyl ester [(S)-NIFE]. Baseline separation of the derivatives was achieved on an ACQUITY UPLC BEH C 18 column (2.1 mm×50mm, 1.7μm). The mobile phase consisted of acetonitrile and water (containing 8mM ammonium hydrogen carbonate) and the flow rate was 0.6mLmin -1 . The derived analytes were sensitively detected by multiple reaction monitoring in the positive ion mode. The lower limits of quantitation ranged from 0.06 to 10ngmL -1 with excellent linearity (r≥0.9909). The intra- and inter-day RSD were in the range of 3.6-12% and 5.7-12%, respectively. The recovery rate was 82.5%-95.3%. With this UPLC-MS/MS method, the 11 d-amino acids in hippocampus, cerebral cortex, olfactory bulb and cerebellum from Alzheimer's disease rats and age-matched controls could be simultaneously determined. Compared with the normal controls, the concentrations of d-serine, d-alanine, d-leucine, and d-proline in hippocampus and cerebral cortex of Alzheimer's disease rat brain were significantly decreased, while no differences in olfactory bulb and cerebellum of all the d-amino acids were observed. The different amounts and distribution of d-amino acids in brain between the two groups, which regulated by particular pathological changes of Alzheimer's disease, would give new insights into further study in neuropathogenesis and provide novel therapeutic targets of Alzheimer

  5. Nicotinic Acetylcholine Receptors in the Pathophysiology of Alzheimer's Disease

    DEFF Research Database (Denmark)

    Thomsen, Morten Skøtt; Andreasen T., Jesper; Arvaniti, Maria

    2016-01-01

    Nicotinic acetylcholine receptors (nAChRs) have been pursued for decades as potential molecular targets to treat cognitive dysfunction in Alzheimer's disease (AD) due to their positioning within regions of the brain critical in learning and memory, such as the prefrontal cortex and hippocampus...

  6. Cerebrospinal Fluid Biomarkers in Diagnosing Alzheimer's Disease in Clinical Practice

    DEFF Research Database (Denmark)

    Slats, Diane; Spies, Petra E; Sjögren, Magnus J C

    2010-01-01

    Analysis of the brain specific biomarkers amyloid beta(42) (Abeta(42)) and total tau (t-tau) protein in cerebrospinal fluid (CSF) has a sensitivity and specificity of more than 85% for differentiating Alzheimer's Disease (AD) from non-demented controls. International guidelines are contradictory...

  7. Autonomic Dysfunction in Patients with Mild to Moderate Alzheimer's Disease

    DEFF Research Database (Denmark)

    Jensen-Dahm, Christina; Waldemar, Gunhild; Staehelin Jensen, Troels

    2015-01-01

    BACKGROUND: Autonomic function has received little attention in Alzheimer's disease (AD). AD pathology has an impact on brain regions which are important for central autonomic control, but it is unclear if AD is associated with disturbance of autonomic function. OBJECTIVE: To investigate autonomic...

  8. Cerebral hemodynamic difference between early- and late-onset Alzheimer's disease by circumferential profile analysis with 123I-IMP brain SPECT

    International Nuclear Information System (INIS)

    Arai, Hisayuki; Hanyu, Haruo; Abe, Shinei; Asano, Tetsuichi; Takasaki, Masaru; Suzuki, Takanari; Abe, Kimihiko; Katsunuma, Hideyo.

    1992-01-01

    We conducted investigation to determine whether early- and late-onset Alzheimer's diseases differ pathophysiologically. Five patients with the early-onset (65 years and under) of the disease and 11 with the late-onset (65 years and over) of the disease were studied by single photon emission CT (SPECT) with N-isopropyl-p-[ 123 I]iodoamphetamine (IMP). Circumferential profile analysis (CPA) was performed to examine differences in the predominant hypoperfusion in the temporoparietal lobe, which is considered to be functionally damaged the most in Alzheimer's disease. The Xm values, calculated from gradients between the motorsensory or occipital cortices and temporoparietal cortex in the circumferential profile curve, were compared in both groups. The Xm values for patients with early- and late-onset Alzheimer's disease were 6.81±2.10 (counts/degree) and 3.28±1.58, respectively, the difference being significant. Our results suggest that functional abnormalities in the temporoparietal area severer in early- than late-onset Alzheimer's disease and that the application of CPA to IMP SPECT is useful to elucidate the pathophysiological difference between each of the disease. (author)

  9. Visual system manifestations of Alzheimer's disease.

    Science.gov (United States)

    Kusne, Yael; Wolf, Andrew B; Townley, Kate; Conway, Mandi; Peyman, Gholam A

    2017-12-01

    Alzheimer's disease (AD) is an increasingly common disease with massive personal and economic costs. While it has long been known that AD impacts the visual system, there has recently been an increased focus on understanding both pathophysiological mechanisms that may be shared between the eye and brain and how related biomarkers could be useful for AD diagnosis. Here, were review pertinent cellular and molecular mechanisms of AD pathophysiology, the presence of AD pathology in the visual system, associated functional changes, and potential development of diagnostic tools based on the visual system. Additionally, we discuss links between AD and visual disorders, including possible pathophysiological mechanisms and their relevance for improving our understanding of AD. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  10. Alzheimer's Disease Facts and Figures

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    Full Text Available ... and older (10 percent) has Alzheimer's dementia. Almost two-thirds of Americans with Alzheimer's are women. Older ... 34 percent) is age 65 or older. Approximately two-thirds of caregivers are women; more specifically, over ...

  11. Alzheimer's Disease Facts and Figures

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  12. Alzheimer's Disease Facts and Figures

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    Full Text Available ... advocate SPECIAL REPORT: FINANCIAL AND PERSONAL BENEFITS OF EARLY DIAGNOSIS Early diagnosis of Alzheimer's provides a number ... a researcher Message boards Get the facts 10 warning signs & symptoms What is dementia What is Alzheimer's ...

  13. Alzheimer's Disease Facts and Figures

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  14. Alzheimer's Disease Facts and Figures

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  15. Alzheimer's Disease Facts and Figures

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    Full Text Available ... to have Alzheimer's or other dementias as older whites. Hispanics are about one and one-half times ... to have Alzheimer's or other dementias as older whites. As the number of older Americans grows rapidly, ...

  16. Alzheimer's Disease Facts and Figures

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  17. Alzheimer's Disease Facts and Figures

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  18. Alzheimer's Disease Facts and Figures

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  20. Alzheimer's Disease Facts and Figures

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    Full Text Available ... care. Caring for someone with Alzheimer's? Get Resources Cost to Nation Alzheimer's places a huge burden on the health care system, with annual costs exceeding a quarter of a trillion dollars. In ...