Histone modifications: Key players in Alzheimer's disease

Alzheimer's disease (AD) is one of the most prevalent diseases in the older population. AD causes progressive cognitive and behavioral impairment, but current treatments are unable to slow or prevent the progression of this disease. Thus, identification of novel biomarkers and therapeutic targets is urgently needed. We previously described the roles of histone acetylation, crotonylation, and lactylation in the accumulation of amyloid beta and hyperphosphorylation of Tau protein, which are the hallmarks of AD. In this review, we summarize and discuss the current knowledge of the role of histone modifications in AD, with a particular emphasis on its association with characterized pathological alterations, including amyloid plaques, Tau tangles, neuroinflammation, and synaptic dysfunction. This review provides novel insights into the central role of histone modifications in AD pathogenesis and evaluates histone-modifying enzymes as potential therapeutic targets for the treatment of AD.