1. School of Pharmacy,Qiqihar Medical University,Qiqihar 161006,China2. Affiliated Third Hospital,Qiqihar Medical University,Qiqihar 161006,China

Corresponding author: YANG HONGYAN, yhycicy@163.com

DOI: 10.12201/bmr.202407.00036

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  Abstract: Objective Using the weighted gene co-expression network analysis (WGCNA) to explore the key genes of aging associated with Alzheimers disease (AD). Methods GSE132903 was selected from GEO database as the analysis dataset. The differential expressed genes (DEGs) of AD were screened, and visualized with volcano and heat map. Aging related genes (ASAGs) were downloaded from MsigDB, Aging Altas and CellAge databases. WGCNA screened the gene modules with the highest correlation with AD, and genes of key modules subsequently performed with gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The key module genes were intersected with differential genes and aging genes to obtain AD age-related differential expressed genes (ARDEGs). Protein-protein interaction (PPI) network analysis was performed using the STRING database to find key node genes. The co-expression networks and associated functions of key genes were analyzed using the GeneMANIA database. The key genes were validated in Alzdata database. Results 226 DEGs (78 up-regulated, 148 down-regulated) and 606 ASAGs were obtained. WGCNA screened out the black-gray modules with high correlation with the clinical characteristics of AD, and obtained 105 key candidate genes. The candidate gene was intersected with differential gene and aging gene to obtain 8 ARDEGs. The top 5 key genes selected by PPI were SYP, STXBP1, VAMP2, CPLX1 and STX1A. Alzdata database verified that the expressions of 5 key genes in other brain regions of AD were down-regulated, except for no significant changes of VAMP2 in hippocampus and STXBP1 in frontal cortex, as well as no expression of CPLX1 in frontal cortex. The differential expression of VAMP2, STXBP1 and STX1A appeared in the early stage of AD, and CPLX1 was related to the pathological process of Tau. SYP and STXBP1 were related to the pathological processes of Aβ and Tau. Conclusion SYP, STXBP1, VAMP2, CPLX1 and STX1A are AD age-related differential expressed genes, which are expected to be potential diagnostic and therapeutic targets for AD.

  Key words: Alzheimers disease, Weighted gene co-expression network analysis, Aging genes, Key genes, Bioinformatics; ; ; ; 

  Submit time: 17 July 2024

  Copyright: The copyright holder for this preprint is the author/funder, who has granted biomedRxiv a license to display the preprint in perpetuity.
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