Dynamics of N6-methyladenosine modification during Alzheimer's disease development

Abstract N6-methyladenosine (m6A) modification is a common RNA modification in the central nervous system and has been linked to various neurological disorders, including Alzheimer's disease (AD). However, little is known about the dynamic of mRNA m6A modification and m6A enzymes during the development of AD.Therefore, this study examined the expression profiles of m6A and its enzymes in the development of AD. The results showed that changes in the expression levels of m6A regulatory factors occurred in the early stages of AD, indicating the potential involvement of m6A modification in disease onset. Moreover, the analysis of mRNA m6A expression profiles using m6A-seq revealed significant differences in m6A modification between AD and control brains.The differentially methylated genes were enriched in GO and KEGG terms related to processes such as inflammation response, immune system processes. And the differently expressed genes (DEGs) are negative associated with microglia homeostasis genes and but positive for “disease-associated microglia” (DAM) associated genes, suggesting that dysregulation of mRNA m6A modification may contribute to the development of AD by affecting the function and gene expression of microglia.