Research Paper Volume 13, Issue 21 pp 24086—24100

Identification of the function and mechanism of m6A reader IGF2BP2 in Alzheimer’s disease

Yanyao Deng1, , Hongwei Zhu2, , Le Xiao1, , Chao Liu1, , Ya-Lin Liu2,3, &, , Wenzhe Gao2, ,

  • 1 Department of Neurology, The First Hospital of Changsha, Changsha, Hunan Province, China
  • 2 Department of Hepatopancreatobiliary Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan Province, China
  • 3 Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China

Received: July 1, 2021       Accepted: October 3, 2021       Published: October 27, 2021
How to Cite

Copyright: © 2021 Deng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Alzheimer’s disease, the most common form of dementia in the elderly, is a kind of neurodegenerative disease. However, its pathogenesis and diagnosis remain unclear. M6A is related to nervous system development and neurodegenerative diseases. Here in this study, using multiple RNA-seq datasets of Alzheimer’s brain tissues, along with bioinformatic analysis, we innovatively found that m6A reader protein IGF2BP2 was abnormally highly expressed in Alzheimer’s patients. After compared between Alzheimer’s and normal brain samples, and between IGF2BP2- high and IGF2BP2- low subgroups of Alzheimer’s patients, we took the shared differentially expressed genes as the relevant gene sets of IGF2PB2 affecting Alzheimer’s disease occurrence for subsequent analysis. Then, weight gene correlation analysis was conducted and 17 functional modules were identified. The module that most positively correlated with Alzheimer’s disease and IGF2PB2-high subgroups were mainly participated in ECM receptor interaction, focal adhesion, cytokine-cytokine receptor interaction, and TGF-beta signaling pathway. Afterwards, a hub gene-based model including 20 genes was constructed by LASSO regression and validated by ROC curve for Alzheimer diagnosis. Finally, we preliminarily elucidated that IGF2BP2 could bind with mRNAs in a m6A-dependent manner. This study first elucidates the pathogenic role of IGF2BP2 in Alzheimer’s disease. IGF2BP2 and its relevant m6A modifications are potential to be new diagnostic and therapeutic targets for Alzheimer’s patients.


AD: Alzheimer’s disease; DEG: differentially expressed gene; WGCNA: weight gene correlation analysis; m6A: N6-methyladenosine; IGF2BP2: Insulin-like growth factor 2 mRNA binding protein 2; GEO: Gene Expression Omnibus; FDR: false discovery rate; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; GSEA: Gene set enrichment analysis; LASSO: least absolute shrinkage and selection operator.