Abstract:Objective: To investigate the differentially expressed genes (DEGs) in different stages of Alzheimer’s disease (AD) through a bioinformatics analysis and the pathogenesis of AD at the molecular level, and to provide new ideas for the research on AD. Methods: The microarray dataset GSE28146 was downloaded from gene expression omnibus (GEO), and the GEO2R online software was used to screen out DEGs between the control group and the mild/moderate/severe AD groups. The DAVID database was used to perform genetic ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEGs, the STRING database was used to establish a protein-protein interaction network, and the Cytoscape software was used to screen out the hub genes. Results: A total of 881, 896, and 1142 DEGs were screened out in the mild, moderate, and severe AD groups, respectively, compared with the control group. The GO functional enrichment analysis showed that the DEGs in the mild AD group were closely associated with the activation of apoptosis-related processes, regulation of immune response, and protein phosphorylation, those in the moderate AD group were closely associated with inflammatory response, apoptosis regulation, and release of calcium ions, and those in the severe AD group were closely associated with the activation of nuclear factor-kappa B, protein phosphorylation and dephosphorylation, and degradation of extracellular matrix. The KEGG analysis showed that the DEGs in the mild AD group were mainly enriched in the p53 and TGF-h signaling pathways, those in the moderate group were mainly involved in the signaling pathways of cancer, natural killer cell-mediated cytotoxicity, and cell adhesion molecules, and those in the severe AD group were mainly enriched in the signaling pathways involving cell cycle, Hippo signaling pathway, and neuroactive ligand-receptor interaction. The protein-protein interaction network analysis showed that the top 5 hub genes with the highest degree of enrichment were GART, EHMT2, KRAS, ESR1, and CD44 in the mild AD group, CBLB, HERC1, UBE2G1, UBE2M, and HECW2 in the moderate AD group, and UBE2C, SOCS3, FBXW7, UBE3B, and UBA6 in the severe AD group. Conclusion: The bioinformatics analysis of different stages of AD shows that the enriched signal pathways and the hub genes may play an important role in the development and progression of AD, which provide a basis and new ideas for further research on AD.
