RNA m6A Methylation and Alzheimer's Disease: Current Evidence and Future Perspectives

Abstract

Background: Alzheimer’s disease (AD) is the most common neurodegenerative disease characterized by the pathological accumulation of b-amyloid and neurofibrillary tangles. Despite substantial progress in both basic and clinical research on AD, the detailed mechanism of AD pathogenesis is still elusive. RNA N6-methyladenosine methylation (m6A) is the most predominant post-transcriptional modification on eukaryotic mRNA, prominently enriched in the mammalian brain. Notably, m6A-modified RNA showed significant changes during the development of AD, indicating an important role of this modification in AD pathogenesis. Aim: In this study, we aim to provide a summary of recent advances highlighting the indispensable role of m6A in AD pathogenesis. Result: From the perspective of m6A modification, we review our current understanding of the association between RNA m6A machinery and the risk factors of AD, as well as its involvement in various pathophysiological hallmarks of AD. We also discuss the main obstacles in current studies about m6A in AD pathogenesis and the corresponding caveats and solutions to them. Conclusion: This review emphasizes the significance of investigating m6A in the context of AD and highlights the considerable potential for m6A to emerge as a novel therapeutic target for AD.