Identification and Validation of Aging-Related Genes in Alzheimer’s Disease

Abstract

Aging is recognized as the key risk factor for Alzheimer’s disease (AD). This study aimed to identify and verify potential aging-related genes associated with AD using bioinformatics analysis. Aging-related differential expression genes (ARDEGs) were determined by the intersection of limma test, weighted correlation network analysis (WGCNA), and 1153 aging and senescence-associated genes. Potential biological functions and pathways of ARDEGs were determined by GO, KEGG, GSEA, and GSVA. Then, LASSO algorithm was used to identify the hub genes and the diagnostic ability of the five ARDEGs in discriminating AD from the healthy control samples. Further, the correlation between hub ARDEGs and clinical characteristics was explored. Finally, the expression level of the five ARDEGs was validated using other four GEO datasets and blood samples of patients with AD and healthy individuals. Five ARDEGs (GFAP, PDGFRB, PLOD1, MAP4K4, and NFKBIA) were obtained. For biological function analysis, aging, cellular senescence, and Ras protein signal transduction regulation were enriched. Diagnostic ability of the five ARDEGs in discriminating AD from the control samples demonstrated a favorable diagnostic value. Eventually, quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) validation test revealed that compared with healthy controls, the mRNA expression level of PDGFRB, PLOD1, MAP4K4, and NFKBIA were elevated in AD patients. In conclusion, this study identified four ARDEGs (PDGFRB, PLOD1, MAP4K4, and NFKBIA) associated with AD. They provide an insight into potential novel biomarkers for diagnosing AD and monitoring progression.