Heliyon (Mar 2024)

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

  • Shuai Gao,
  • Yuqing Wang,
  • Xiaoyu Li,
  • Yuqing Liang,
  • Zhihao Jin,
  • Baozhi Yang,
  • Ti-Fei Yuan,
  • Hengli Tian,
  • Bo Peng,
  • Yanxia Rao

Journal volume & issue
Vol. 10, no. 6
p. e26911

Abstract

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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, the dynamic of mRNA m6A modification and m6A enzymes during the development of AD are not well understood. 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 occur in the early stages of AD, indicating a potential role for m6A modification in the onset of the disease. Additionally, the analysis of mRNA m6A expression profiles using m6A-seq revealed significant differences in m6A modification between AD and control brains. The genes with differential methylation were found to be enriched in GO and KEGG terms related to processes such as inflammation response, immune system processes. And the differently expressed genes (DEGs) are negatively lryassociated with genes involved in microglia hemostasis, but positively associated with genes related to “disease-associated microglia” (DAM) associated genes. These findings suggest that dysregulation of mRNA m6A modification may contribute to the development of AD by affecting the function and gene expression of microglia.

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