Objective To identify core genes of Alzheimer's disease (AD) through bioinformatic analysis and explore potential pathogenic signaling pathways.

Methods Gene expression profiling data related to AD were downloaded from the Gene Expression Omnibus (GEO) database, with datasets GSE227221 and GSE162873 selected for analysis. GEO2R online analysis software was applied to screen differentially expressed genes (DEGs) between AD tissue samples and normal brain tissue samples. The Disease Ontology (DO) enrichment analysis of DEGs was performed using the DOSE package in R software, while Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted through the online data analysis tool DAVID. Protein-protein interactions (PPI) among genes were analyzed using the STRING database, and a PPI network was constructed with Cytoscape software. Hub genes within the PPI network were identified and screened using the MCODE plugin. Based on MCODE scores, further analysis was conducted to select core genes.

Results A total of 1, 373 DEGs with consistent expression trends involved in the onset and progression of AD were identified from the two datasets, with the core genes of GIMAP genes (including GIMAP1, GIMAP4, GIMAP5, GIMAP6, GIMAP7, and GIMAP1-GIMAP5). DO enrichment analysis revealed the strongest associations between DEGs and three diseases: systemic lupus erythematosus, lupus erythematosus, and atherosclerosis. GO functional enrichment analysis indicated that DEGs were primarily enriched in three signaling pathways: the classical Wnt signaling pathway, phospholipase C-activated G protein-coupled receptor pathway, and plasma membrane lateral domain pathway. KEGG pathway enrichment analysis showed that DEGs were primarily enriched in pathways such as cytokine-cytokine receptor interaction, neuroactive ligand-receptor interaction, and cancer-related transcriptional dysregulation.

Conclusion The core pathogenic gene of AD may be the GIMAP gene, and the associated pathways are complex, potentially implicating immune dysfunction.