Epigenome-wide study uncovers large-scale changes in histone acetylation driven by tau pathology in aging and Alzheimer's human brains.

ABSTRACT: Accumulation of tau and amyloid-β are two pathologic hallmarks of Alzheimer's disease. We conducted an epigenome-wide association study using the histone 3 lysine 9 acetylation (H3K9ac) mark in 669 aged human prefrontal cortices; in contrast with amyloid-β, tau protein burden had a broad effect on the epigenome, affecting 5,990 of 26,384 H3K9ac domains. Tau-related alterations aggregated in large genomic segments reflecting spatial chromatin organization, and the magnitude of these effects correlated with the segment's nuclear lamina association. Functional relevance of these chromatin changes was demonstrated by (1) consistent transcriptional changes in three independent datasets and (2) similar findings in two mouse models of Alzheimer's disease. Finally, we found that tau overexpression

SUBMITTER: Klein HU 

PROVIDER: S-EPMC6516529 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature