Objective Using the weighted gene co-expression network analysis(WGCNA)to explore the key genes of aging associated with Alzheimer's 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 and senescence-associated 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.AD age-related differential expressed genes(ARDEGs)were obtained by taking intersection genes of DEGs,key module genes of WGCNA and ASAGs.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,606 ASAGs and 8 ARDEGs were obtained.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 amyloid β-protein and Tau.Conclusion SYP,STXBP1,VAMP2,CPLX1 and STX1A are ARDEGs,which are expected to be potential diagnostic and therapeutic targets for AD.