Effect of APOE alleles on the glial transcriptome in normal aging and Alzheimer's disease.

ABSTRACT: The roles of APOEε4 and APOEε2-the strongest genetic risk and protective factors for Alzheimer's disease-in glial responses remain elusive. We tested the hypothesis that APOE alleles differentially impact glial responses by investigating their effects on the glial transcriptome from elderly control brains with no neuritic amyloid plaques. We identified a cluster of microglial genes that are upregulated in APOEε4 and downregulated in APOEε2 carriers relative to APOEε3 homozygotes. This microglia-APOE cluster is enriched in phagocytosis-including TREM2 and TYROBP-and proinflammatory genes, and is also detectable in brains with frequent neuritic plaques. Next, we tested these findings in APOE knock-in mice exposed to acute

SUBMITTER: Serrano-Pozo A 

PROVIDER: S-EPMC9531903 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature