Cell type-specific histone acetylation profiling of Alzheimer's disease subjects and integration with genetics.
Level 4 - case-series / case-control
Post-mortem case-control tissue profiling study.
PubMed 36683855 · doi:10.3389/fnmol.2022.948456
What was done
Genome-wide histone 3 lysine 27 acetylation (H3K27ac) was profiled across three major brain cell types isolated from the hippocampus and dorsolateral prefrontal cortex of post-mortem human subjects with and without Alzheimer's disease. The epigenomic data were integrated with late-onset Alzheimer's disease risk variants to assess differential acetylation associations with age and amyloid-β load.
What was found
The abstract reports no numerical values, sample sizes, or effect estimates. Late-onset Alzheimer's disease risk SNPs colocalized strongly with microglia-specific regulatory elements. Microglia showed more H3K27ac changes associated with age than with amyloid-β load. In contrast, an oligodendrocyte-enriched glial population harbored the majority of differentially acetylated peaks associated with amyloid-β load, which were located near early-onset risk genes (APP, PSEN1, PSEN2), late-onset risk loci (BIN1, PICALM, CLU, ADAM10, ADAMTS4, SORL1, FERMT2), amyloid processing genes (BACE1), and genes involved in myelination and oligodendrocyte development.
Why it matters
These findings suggest that oligodendrocyte gene dysregulation and myelin deregulation play a key role in mediating Alzheimer's risk and pathology alongside established microglial pathways.
Limits
Sample size, donor demographics, and quantitative statistics (such as effect sizes and p-values) are omitted from the abstract. The cross-sectional post-mortem design cannot establish causality between histone acetylation changes and amyloid-β pathology, and analysis was limited to three cell types in two brain regions.
Cited by
- supports Epigenetic profiling of Alzheimer's disease brains reveals widespread epigenetic changes in both microglia and oligodendrocytes.