Epigenetic Regulation in Alzheimer’s Disease: Roles of DNA Methylation and Histone Regulation

Abstract

A l z h e i m e r ’s d i s e a s e ( A D ) i s a p r o g r e s s i v e neurodegenerative disorder and one of the leading causes of dementia. The most significant known risk factor for AD is aging, and the increasing number of elderly people in low- and middle-income countries leads to an increase in AD incidence. Increasingly, age-related epigenetic changes are recognized as key drivers of the onset and progression of AD. This review examines how epigenetic processes, including DNA methylation and histone modification, affect amyloid-beta (Aβ) generation and clearance and tau protein pathology development, which are the two main features of AD. The genes APP, BACE1, PSEN1, and APOE show abnormal DNA methylation patterns, which result in elevated Aβ production and reduced clearance mechanisms. Alterations in histone acetylation and methylation patterns lead to synaptic dysfunction, which results in memory problems. The study demonstrates that BACE1 and PSEN1 methylation decrease with age and APOE status, which leads to Aβ accumulation. Hippocampal regions show decreased histone acetylation, which blocks vital gene expression required for learning, and tau accumulation results from methylation changes that damage cellular cleaning systems. These findings reveal the significant role of epigenetic processes in AD. A deeper understanding of these mechanisms not only sheds light on disease progression but also opens new pathways for treatment. This review highlights promising epigenetic targets and current challenges, encouraging the continued development of epigenetics-based therapies for AD and related neurodegenerative conditions.