Abstract: Objective To preliminarily explore the potential molecular mechanism of Alzheimer disease (AD) using bioinformatics methods. Methods Differentially expression genes (DEGs) in GSE5281 and GSE132903 datasets were identified using GEO2R,and then systematically analyzed using online Matescape,STRING and Cytoscape softwares. The resultant key genes were further validated in AD mice by qPCR. Results A total of 250 overlapping DEGs were obtained from two datasets. The resultant DEGs mainly focused on synaptic transmission and neuronal system. A protein-protein interaction (PPI) network of DEGs was constructed,while four hub genes were identified,including synaptosomal-associated protein 25 (SNAP25),synapsin I (SYN1),gamma-aminobutyric acid s receptor subunit gamma 2 (GABRG2),and synaptotagmin 4 (SYT4). Conclusions The pathogenesis of AD is closely related to SNAP25,SYN1,GABRG2,and SYT4 genes,which are mainly involved in synaptic neurotransmitter release processes. These findings will provide deepened understanding for molecular mechanism of AD,and give new thoughts for developing potential targets for new drugs and early diagnosis and treatment of AD.