The impact of epigenetic and epitranscriptomic modifications on Alzheimer's disease: the mysteries of DNA, RNA, and histone methylation

Abstract

AD (Alzheimer's disease) is a neurodegenerative disorder of the CNS (Central Nervous System) characterized by progressive memory decline, significantly impairing patients' quality of life and representing the most common cause of dementia. However, the exact etiology of AD remains unclear and is likely influenced by the interplay of genetic, lifestyle, and environmental factors. Therefore, extensive research efforts are urgently needed to unravel the complex mechanisms underlying the onset and progression of AD. Increasing evidence has highlighted the pivotal role of alterations in epigenetics and epitranscriptomics in AD pathogenesis. Among these, methylation modifications, as crucial regulators of epigenetic and epitranscriptomic processes, contribute to disease development by affecting gene expression, chromatin structure, and RNA-related processes such as splicing, transport, translation, and degradation. Thus, an in-depth exploration of the relationship between methylation modifications and AD is critical for elucidating disease mechanisms and identifying novel therapeutic targets. This review provides a comprehensive overview of the impacts of epigenetic and epitranscriptomic modifications-including DNA methylation, histone methylation, and m6A (N6-methyladenosine) modifications-on AD pathogenesis, as well as the roles of aberrant epigenetic regulation of related genes in the disease. The aim is to enhance understanding of the regulatory mechanisms linking epigenetics and epitranscriptomics to AD pathogenesis, ultimately promoting the development of more targeted therapeutic strategies and approaches.

Keywords: Alzheimer’s disease (AD); DNA methylation; Epigenetics; Epitranscriptomics; Histone methylation; Methylation modifications; N6-methyladenosine (m6A).