This article explores the epigenomic and transcriptomic changes in Alzheimer's disease (AD) progression and cognitive resilience, utilizing single-cell multi-region analysis across six brain areas. The authors reveal widespread epigenomic relaxation and information loss in AD, particularly in vulnerable neurons and exhausted glial cells. Conversely, preserved epigenomic stability is shown to correlate with better cognitive function and resilience. The study identifies key genes and regulatory networks associated with these epigenomic dynamics, offering potential insights for therapeutic strategies targeting AD.

References:

• Liu Z, Zhang S, James B T, et al. Single-cell multiregion epigenomic rewiring in Alzheimer’s disease progression and cognitive resilience[J]. Cell, 2025.