Identification Of Key Molecular Targets And Therapeutic Interventions In Alzheimer's Disease: An Integrative Analysis Of Differentially Expressed Genes And Regulatory Drugs

Alzheimer’s disease (AD) is a complex neurodegenerative disorder lacking effective diagnostic and therapeutic options. This study utilized bioinformatics analyses on two GEO datasets (GSE29378 and GSE48350) to identify key differentially expressed genes (DEGs) in AD, followed by validation in GSE5281. Protein-protein interaction (PPI) network analysis revealed four hub genes—CLK4, SNTB1, EFCAB1, and TSPAN1. Expression analysis showed that CLK4, SNTB1, and EFCAB1 were significantly downregulated in AD, while TSPAN1 exhibited a slight upregulation. Receiver Operating Characteristic (ROC) analysis demonstrated high diagnostic accuracy for these genes, with AUC values of 0.99, 0.98, 0.96, and 0.95, respectively, highlighting their potential as AD biomarkers. Gene enrichment analysis revealed associations with critical pathways, including the "Hippo signaling pathway," "AGE-RAGE signaling pathway," and "TNF signaling pathway," suggesting roles in immune response, transcriptional regulation, and cellular stress response in AD pathology. Drug sensitivity analysis using the GSCA database identified TSPAN1 as associated with resistance to several drugs, including doxorubicin, indicating its potential role in AD drug resistance. In contrast, CLK4, SNTB1, and EFCAB1 showed minimal correlation with drug response, implying their primary involvement in disease pathogenesis. Collectively, these findings suggest that CLK4, SNTB1, and EFCAB1 are promising diagnostic markers, while TSPAN1 may serve as a therapeutic target to overcome drug resistance. This study highlights novel molecular insights into AD, providing a foundation for future research on precision diagnostics and therapies.