A histone acetylome-wide association study of Alzheimer's disease identifies disease-associated H3K27ac differences in the entorhinal cortex.
Level 4 - case-series / case-control
Case-control study of post-mortem human brain tissue
PubMed 30349106 · doi:10.1038/s41593-018-0253-7
What was done
Researchers profiled genome-wide histone 3 lysine 27 acetylation (H3K27ac) in post-mortem entorhinal cortex samples from Alzheimer's disease (AD) cases and matched controls using chromatin immunoprecipitation and high-throughput sequencing. They analyzed differential acetylation peaks, biological pathway enrichment, partitioned heritability against AD genetic risk loci, and correlation with proximal gene expression.
What was found
The authors identified 4,162 differentially acetylated H3K27ac peaks between AD cases and controls (false discovery rate < 0.05). Differentially acetylated regions were enriched for pathways related to amyloid-β and tau pathology (including APP, PSEN1, PSEN2, and MAPT) and overlapped with late-onset AD risk variants. Partitioned heritability showed significant enrichment of AD risk variants in entorhinal cortex H3K27ac peaks. Differential acetylation was also associated with altered transcription of nearby genes, including CR1, GPR22, KMO, PIM3, PSEN1, and RGCC. Numerical effect sizes and specific sample counts were not reported in the abstract.
Why it matters
This study provides an epigenome-wide map of histone acetylation in vulnerable brain tissue, demonstrating that epigenetic alterations in regulatory chromatin regions correlate with both genetic susceptibility loci and pathological gene expression in Alzheimer's disease.
Limits
The abstract does not state the sample size (n), clinical staging, or post-mortem tissue quality metrics. Because this is an observational study of post-mortem tissue, it cannot establish whether histone acetylation changes cause disease progression or occur as secondary consequences of cell loss and neurodegeneration.
Cited by
- supports In a 2018 study, widespread histone acetylation changes were found in the entorhinal cortex of Alzheimer's disease brains.