Abstract
Mounting evidence highlights the crucial role of aging in the pathogenesis of Alzheimer's disease (AD). We have previously explored human apoE-targeted replacement mice across different ages and identified distinct molecular pathways driven by aging. However, the specific contribution of different brain cell types to the gene modules underlying these pathways remained elusive. To bridge this knowledge gap, we employed a computational deconvolution approach to examine cell-type-specific gene expression profiles in major brain cell types, including astrocytes (AS), microglia (MG), oligodendroglia (OG), neurons (NEU), and vascular cells (VC). Our findings revealed that immune module genes were predominantly expressed in MG, OG, and VC. The lipid metabolism module genes were primarily expressed in AS, MG, and OG. The mitochondria module genes showed prominent expression in VC, and the synapse module genes were primarily expressed in NEU and VC. Furthermore, we identified intra- and inter-cell-type interactions among these module genes and validated their aging-associated expression changes using published single cell studies. Our study dissected bulk brain transcriptomics data at the cellular level, providing a closer examination of the cell-type contributions to the molecular pathways driven by aging.
Original language | English |
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Article number | 16855 |
Journal | Scientific Reports |
Volume | 13 |
Issue number | 1 |
DOIs | |
State | Published - Dec 2023 |
Bibliographical note
Publisher Copyright:© 2023, Springer Nature Limited.
Funding
This work was supported by NIH grants U19AG069701 (to Y.R., Y.W.A., and N.Z.), RF1AG046205 (to N.Z.), and R01AG66395 (to N.Z.); and a BrightFocus Foundation grant (to N.Z.).
Funders | Funder number |
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National Institutes of Health (NIH) | R01AG66395, U19AG069701, RF1AG046205 |
National Institutes of Health (NIH) | |
BrightFocus Foundation |
ASJC Scopus subject areas
- General