Abstract:

Objective To screen the differentially expressed genes（DEG） and signal pathways related to Alzheimer's disease（AD） using bioinformatics analysis methods based on GEO database. Methods GSE118553 was selected from GEO database as the analysis dataset,and GSE106241 was used as the validation dataset of key genes. The DEG were selected from the GSE118553 dataset matrix. Using cluster profile package,Gene Ontology（GO） analysis and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway analysis on DEG were preformed. Protein-protein interaction（PPI） network was constructed to screen out the top 10 key genes involved in AD. GSE106241 dataset was used to verify the expression differences of 10 key genes in temporal cortex tissues of AD patients with different braak grades to healthy controls and the correlation with amyloid bata-protein（Aβ）42 expression. Results There were 157 DEG obtained in GSE118553 dataset,including 88 up-regulated genes and 69 down-regulated genes. GO analysis and KEGG pathway analysis showed that DEG were enriched in gamma-aminobutyric acid（GABA） signaling pathway,neurotransmitter transmission and synaptic transmission and so on. A PPI network of DEG was constructed,and 10 key genes（SNAP25,SYT1,GRIN2A,SLC12A5,GAD1,GABRG2,GABRD,PVALB,GABRB2 and FN1） related to Alzheimer's disease were verified. The GSE106241 dataset was used for verification,and the results showed that there was statistical significance in the expression of SNAP25,SYT1,GRIN2A,SLC12A5,GAD1,GABRG2,GABRD,PVALB and GABRB2 in temporal cortex tissues of AD patients with different braak grades（P<0.05）. Pearson correlation analysis showed that the expression of SNAP25,SYT1 and SLC12A5 were negatively correlated with the expression of Aβ42（r values were -0.354,-0.283 and -0.310,respectively,P<0.05）. Conclusions The obtained key genes,SNAP25,SYT1 and SLC12A5,may be potential biomarkers of Alzheimer's disease and provide new targets for the diagnosis and treatment of AD.

Key words: Alzheimer's disease, Bioinformatics, Hub gene, Signal pathway