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
Affiliations
Shuai Gao
Department of Neurosurgery, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Innovative Center for New Drug Development of Immune Inflammatory Diseases, Ministry of Education, Fudan University, Shanghai, 200040, China
Yuqing Wang
Department of Neurology, Zhongshan Hospital, Department of Laboratory Animal Science, MOE Frontiers Center for Brain Science, Fudan University, Shanghai, 200032, China; Department of Medical Science, Medical College of Jinzhou Medical University, Jinzhou, Liaoning, 121010, China
Xiaoyu Li
Department of Neurosurgery, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Innovative Center for New Drug Development of Immune Inflammatory Diseases, Ministry of Education, Fudan University, Shanghai, 200040, China
Yuqing Liang
Department of Neurology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
Zhihao Jin
Department of Neurology, Zhongshan Hospital, Department of Laboratory Animal Science, MOE Frontiers Center for Brain Science, Fudan University, Shanghai, 200032, China
Baozhi Yang
Department of Neurology, Zhongshan Hospital, Department of Laboratory Animal Science, MOE Frontiers Center for Brain Science, Fudan University, Shanghai, 200032, China
Ti-Fei Yuan
Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 201108, China
Hengli Tian
Department of Neurology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
Bo Peng
Department of Neurosurgery, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Innovative Center for New Drug Development of Immune Inflammatory Diseases, Ministry of Education, Fudan University, Shanghai, 200040, China; Department of Neurology, Jinshan Hospital, Fudan University, Shanghai, 201508, China
Yanxia Rao
Department of Neurology, Zhongshan Hospital, Department of Laboratory Animal Science, MOE Frontiers Center for Brain Science, Fudan University, Shanghai, 200032, China; Corresponding author.
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.
