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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:Granulovacuolar degeneration (GVD) is a common feature in Alzheimer's disease (AD). The occurrence of GVD is closely associated with that of neurofibrillary tangles (NFTs) and GVD is even considered to be a pre-NFT stage in the disease process of AD. Currently, the composition of GVD bodies, the mechanisms associated with GVD and how GVD exactly relates to NFTs is not well understood. By combining immunohistochemistry (IHC) and laser microdissection (LMD) we isolated neurons with GVD and those bearing tangles separately from human post-mortem AD hippocampus (n = 12) using their typical markers casein kinase (CK)1δ and phosphorylated tau (AT8). Control neurons were isolated from cognitively healthy cases (n = 12). 3000 neurons per sample were used for proteome analysis by label free LC-MS/MS. In total 2596 proteins were quantified across samples and a significant change in abundance of 115 proteins in GVD and 197 in tangle bearing neurons was observed compared to control neurons. With IHC the presence of PPIA, TOMM34, HSP70, CHMP1A, TPPP and VXN was confirmed in GVD containing neurons. We found multiple proteins localizing specifically to the GVD bodies, with VXN and TOMM34 being the most prominent new protein markers for GVD bodies. In general, protein groups related to protein folding, proteasomal function, the endolysosomal pathway, microtubule and cytoskeletal related function, RNA processing and glycolysis were found to be changed in GVD neurons. In addition to these protein groups, tangle bearing neurons show a decrease in ribosomal proteins, as well as in various proteins related to protein folding. This study, for the first time, provides a comprehensive human based quantitative assessment of protein abundances in GVD and tangle bearing neurons. In line with previous functional data showing that tau pathology induces GVD, our data support the model that GVD is part of a pre-NFT stage representing a phase in which proteostasis and cellular homeostasis is disrupted. Elucidating the molecular mechanisms and cellular processes affected in GVD and its relation to the presence of tau pathology is highly relevant for the identification of new drug targets for therapy.

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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