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Relative neuron loss in hippocampal sclerosis of aging and Alzheimer's disease.

ABSTRACT: OBJECTIVE:To characterize the pattern of neuron loss in hippocampal sclerosis of aging (HS-Aging) and age-related diseases and to evaluate its contribution to cognitive impairment in the elderly. METHODS:Participants (n?=?1,361) came from longitudinal observational studies of aging at the Knight Alzheimer Disease Research Center, Washington University (St. Louis, MO). Relative neuron loss in the hippocampus of HS-Aging was measured using unbiased stereological methods. Transactive response DNA-binding protein of 43 kDa (TDP-43) proteinopathy, a putative marker of HS-Aging, was assessed. Clinical and cognitive data were analyzed using parametric statistical methods. RESULTS:Ninety-three cases had HS-Aging (6.8%), 8 cases had "pure" HS-Aging, and 37 cases had comorbid intermediate or high Alzheimer's disease neuropathological change (i/h ADNC). Relative neuron loss (ratio of neuron number in hippocampal subfield CA1 to the neuron number in parahippocampal gyrus) was 0.15 for HS-Aging; this was significantly lower than 0.64 for i/h ADNC and 0.66 for control cases (Kruskal-Wallis test, p?

SUBMITTER: Ihara R

PROVIDER: S-EPMC6373729 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Relative neuron loss in hippocampal sclerosis of aging and Alzheimer's disease.

Ihara Ryoko R Vincent Benjamin D BD Baxter Michael R MR Franklin Erin E EE Hassenstab Jason J JJ Xiong Chengjie C Morris John C JC Cairns Nigel J NJ

Annals of neurology 20181025 5

<h4>Objective</h4>To characterize the pattern of neuron loss in hippocampal sclerosis of aging (HS-Aging) and age-related diseases and to evaluate its contribution to cognitive impairment in the elderly.<h4>Methods</h4>Participants (n = 1,361) came from longitudinal observational studies of aging at the Knight Alzheimer Disease Research Center, Washington University (St. Louis, MO). Relative neuron loss in the hippocampus of HS-Aging was measured using unbiased stereological methods. Transactive ...[more]

PMID: 30246887

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Project description:To evaluate molecular signatures of an individual cell type in comparison to the associated region relevant towards understanding the pathogenesis of Alzheimer's disease (AD), CA1 pyramidal neurons and the surrounding hippocampal formation were microaspirated via laser capture microdissection (LCM) from neuropathologically confirmed AD and age-matched control (CTR) subjects as well as from wild type mouse brain using single population RNA amplification methodology coupled with custom-designed microarray analysis with real-time quantitative polymerase-chain reaction (qPCR) validation. CA1 pyramidal neurons predominantly displayed downregulation of classes of transcripts related to synaptic transmission in AD versus CTR. Regional hippocampal dissections displayed downregulation of several overlapping genes found in the CA1 neuronal population related to neuronal expression, as well as upregulation of select transcripts indicative of admixed cell types including glial-associated markers and immediate-early and cell death genes. Gene level distributions observed in CA1 neurons and regional hippocampal dissections in wild type mice paralleled expression mosaics seen in postmortem human tissue. Microarray analysis was validated in qPCR studies using human postmortem brain tissue and CA1 sector and regional hippocampal dissections obtained from a mouse model of AD/Down syndrome (Ts65Dn mice) and normal disomic (2N) littermates. Classes of transcripts that have a greater percentage of the overall hybridization signal intensity within single neurons tended to be genes related to neuronal communication. The converse was also found, as classes of transcripts such as glial-associated markers were under represented in CA1 pyramidal neuron expression profiles relative to regional hippocampal dissections. These observations highlight a dilution effect that is likely to occur in conventional regional microarray and qPCR studies. Thus, single population studies of specific neurons and intrinsic circuits will likely yield informative gene expression profile data that may be subthreshold and/or underrepresented in regional studies with an admixture of cell types.

Dataset Information

Relative neuron loss in hippocampal sclerosis of aging and Alzheimer's disease.

Publications

Relative neuron loss in hippocampal sclerosis of aging and Alzheimer's disease.

Similar Datasets

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