Screening and Identification of Potential Peripheral Blood Biomarkers for Alzheimer's Disease Based on Bioinformatics...

BACKGROUND Alzheimer's disease (AD) is the leading cause of dementia worldwide; however, the molecular mechanisms underlying its pathogenesis remain unclear. The present study aimed to discover some potential peripheral blood biomarkers for early detection of patients with AD. MATERIAL AND METHODS Publicly available AD datasets - GSE18309 and GSE97760 - were obtained from the Gene Expression Omnibus database, and limma package from Bioconductor was employed to search for differently expressed genes (DEGs). Weighted correlation network analysis was performed to identify DEGs with highly synergistic changes, and functional annotation of DEGs was performed using gene set enrichment analysis and Metascape. STRING and Cytoscape were used to construct protein-protein interaction networks and analyze the most significant hub genes. Thereafter, the Comparative Toxicogenomics Database (CTD) was used to identify hub genes associated with AD pathology, and Connectivity Map was used to screen small molecule drugs for AD. Finally, hub genes coupled with corresponding predicted miRNAs involved in AD were assessed via TargetScan, and functional annotation of predicted miRNAs was performed using DIANA database. RESULTS Our analyses revealed 5042 DEGs; based on functional analyses, these DEGs were mainly associated with oligosaccharide lipid intermediate biosynthetic process, cyclin binding, signaling pathways regulating pluripotency of ubiquitin mediated proteolysis, and extracellular matrix-receptor interaction. UBB, UBA52, SRC, MMP9, VWF, GP6, and PF4 were identified as the hub genes. The CTD showed that these hub genes are closely related with AD or cognition impairment. CONCLUSIONS The identified hub genes and corresponding miRNAs might be useful as potential peripheral blood biomarkers of AD.