Dataset Information

Psychosis in "Cognitively Asymptomatic" Elderly Subjects is Associated With Neuritic Plaque Load, Not Neurofibrillary Tangles.

ABSTRACT: INTRODUCTION:Despite having severe Alzheimer disease pathology, some individuals remain cognitively asymptomatic (cASYM). To explore noncognitive manifestations in these cASYM individuals, we aim to investigate the prevalence and pathologic substrates of psychosis. METHODS:Data were obtained from the National Alzheimer's Coordinating Center. The Neuropsychiatric Inventory Questionnaire, quick version was used to evaluate presence of psychosis. Subjects with Mini-Mental Status Examination score of ?24 with frequent neuritic plaques (NPs) were defined as NPcASYM, and those with Braak and Braak stage of neurofibrillary tangles of V/VI were defined as NTcASYM (both groups collectively designated cASYM). Logistic regression analysis was used to examine the association between NP and neurofibrillary tangle severity and psychosis accounting for potential confounders. RESULTS:We identified 667 subjects with Mini-Mental Status Examination score of ?24, of which 137 were NPcASYM and 96 were NTcASYM. NPcASYM were at significantly higher risk of having psychosis compared with those with moderate or sparse/no NP (odds ratio, 2.47; 95% confidence interval, 1.54-3.96). NTcASYM were also at higher risk compared with those with Braak and Braak stage I to IV, but the association explained by the effect of Lewy body pathology and microinfarcts. DISCUSSION:The load of NP may be an important substrate of psychosis in individuals who show no gross cognitive symptoms.

SUBMITTER: Kim J

PROVIDER: S-EPMC6107422 | biostudies-literature | 2018 Jul-Sep

REPOSITORIES: biostudies-literature

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Psychosis in "Cognitively Asymptomatic" Elderly Subjects is Associated With Neuritic Plaque Load, Not Neurofibrillary Tangles.

Kim Julia J Schweizer Tom A TA Fischer Corinne E CE Munoz David G DG

Alzheimer disease and associated disorders 20180701 3

<h4>Introduction</h4>Despite having severe Alzheimer disease pathology, some individuals remain cognitively asymptomatic (cASYM). To explore noncognitive manifestations in these cASYM individuals, we aim to investigate the prevalence and pathologic substrates of psychosis.<h4>Methods</h4>Data were obtained from the National Alzheimer's Coordinating Center. The Neuropsychiatric Inventory Questionnaire, quick version was used to evaluate presence of psychosis. Subjects with Mini-Mental Status Exam ...[more]

PMID: 29553944

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Project description:Tauopathies are a class of neurodegenerative diseases, including Alzheimer's disease, frontotemporal dementia and progressive supranuclear palsy, which are associated with the pathological aggregation of tau protein into neurofibrillary tangles (NFT). Studies have characterized tau as a "prion-like" protein given its ability to form distinct, stable amyloid conformations capable of transcellular and multigenerational propagation in clonal fashion. It has been proposed that progression of tauopathy could be due to the prion-like propagation of tau, suggesting the possibility that end-stage pathologies, like NFT formation, may require an instigating event such as tau seeding. To investigate this, we applied a novel human induced pluripotent stem cell (hiPSC) system we have developed to serve as a human neuronal model. We introduced the tau repeat domain (tau-RD) with P301L and V337M (tau-RD-LM) mutations into hiPSC-derived neurons and observed expression of tau-RD at levels similar to total tau in postmortem AD brains. Tau aggregation occurred without the addition of recombinant tau fibrils. The conditioned media from tau-RD cultures contained tau-RD seeds, which were capable of inducing aggregate formation in homotypic mode in non-transduced recipient neuronal cultures. The resultant NFTs were thioflavin-positive, silver stain-positive, and assumed fibrillary appearance on transmission electron microscopy (TEM) with immunogold, which revealed paired helical filament 1 (PHF1)-positive NFTs, representing possible recruitment of endogenous tau in the aggregates. Functionally, expression of tau-RD caused neurotoxicity that manifested as axon retraction, synaptic density reduction, and enlargement of lysosomes. The results of our hiPSC study were reinforced by the observation that Tau-RD-LM is excreted in exosomes, which mediated the transfer of human tau to wild-type mouse neurons in vivo. Our hiPSC human neuronal system provides a model for further studies of tau aggregation and pathology as well as a means to study transcellular propagation and related neurodegenerative mechanisms.

Dataset Information

Psychosis in "Cognitively Asymptomatic" Elderly Subjects is Associated With Neuritic Plaque Load, Not Neurofibrillary Tangles.

Publications

Psychosis in "Cognitively Asymptomatic" Elderly Subjects is Associated With Neuritic Plaque Load, Not Neurofibrillary Tangles.

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