AUTHOR=Ramamurthy Easwaran , Welch Gwyneth , Cheng Jemmie , Yuan Yixin , Gunsalus Laura , Bennett David A. , Tsai Li-Huei , Pfenning Andreas R. TITLE=Cell type-specific histone acetylation profiling of Alzheimer’s disease subjects and integration with genetics JOURNAL=Frontiers in Molecular Neuroscience VOLUME=15 YEAR=2023 URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2022.948456 DOI=10.3389/fnmol.2022.948456 ISSN=1662-5099 ABSTRACT=
We profile genome-wide histone 3 lysine 27 acetylation (H3K27ac) of 3 major brain cell types from hippocampus and dorsolateral prefrontal cortex (dlPFC) of subjects with and without Alzheimer’s Disease (AD). We confirm that single nucleotide polymorphisms (SNPs) associated with late onset AD (LOAD) show a strong tendency to reside in microglia-specific gene regulatory elements. Despite this significant colocalization, we find that microglia harbor more acetylation changes associated with age than with amyloid-β (Aβ) load. In contrast, we detect that an oligodendrocyte-enriched glial (OEG) population contains the majority of differentially acetylated peaks associated with Aβ load. These differential peaks reside near both early onset risk genes (