Epigenetic age of the pre-frontal cortex is associated with neuritic plaques, amyloid load, and Alzheimer's disease related cognitive functioning.
Level 4 - case-series / case-control
Cross-sectional postmortem tissue analysis within prospective cohort studies
PubMed 26684672 · doi:10.18632/aging.100864
What was done
The authors measured DNA methylation-based epigenetic age acceleration in postmortem dorsolateral prefrontal cortex (DLPFC) samples from 700 Caucasian participants in the Religious Order Study and the Rush Memory and Aging Project. They evaluated associations between brain epigenetic age acceleration, Alzheimer's disease (AD) neuropathological markers, and longitudinal cognitive decline, and estimated heritability using genetic complex trait analysis (GCTA).
What was found
DLPFC epigenetic age acceleration was weakly but significantly correlated with neuropathological burden: diffuse plaques (r = 0.12, p = 0.0015), neuritic plaques (r = 0.11, p = 0.0036), and amyloid load (r = 0.091, p = 0.016). In individuals with AD, accelerated epigenetic aging was associated with steeper decline in global cognitive functioning (β = -0.500, p = 0.009), episodic memory (β = -0.411, p = 0.009), and working memory (β = -0.405, p = 0.011). GCTA indicated that epigenetic age acceleration in the brain is moderately heritable (h² = 0.41) and genetically correlated with diffuse plaques (r = 0.24, p = 0.010) and working memory (r = -0.35, p = 0.065).
Why it matters
The study demonstrates that epigenetic age acceleration in the human prefrontal cortex is linked to classic AD neuropathology and cognitive deterioration, supporting the epigenetic clock as a molecular biomarker of brain aging.
Limits
The cohort was restricted to Caucasian participants from two specific cohorts, limiting generalizability across diverse ancestries. Postmortem cross-sectional tissue analysis cannot establish causality between epigenetic acceleration and neuropathology, and the observed correlations with pathology were modest (r = 0.09–0.12).
Cited by
- supports Alzheimer's disease cases show epigenetic age acceleration in the prefrontal cortex.