Abstract

BACKGROUND: Alzheimer disease (AD) is a typical progressive and destructive neurodegenerative disease that has been studied extensively. However, genetic features and molecular mechanisms underlying AD remain unclear. Here we used bioinformatics to investigate the candidate nuclear genes involved in the molecular mechanisms of AD.

MATERIAL AND METHODS: First, we used Gene Expression Omnibus (GEO) database to obtain the expression profiles of the mRNAs from hippocampus microarray and identify differentially expressed genes (DEGs) the plier algorithm. Second, functional annotation and visualization of the DEGs were conducted by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Finally, BioGRID, IntAct, STRING, and Cytoscape were utilized to construct a protein-protein interaction (PPI) network. Hub genes were analytically obtained from the PPI network and the microRNA (miRNA)-target network.

RESULTS: Two hippocampus microarrays (GSE5281 and GSE48350) were obtained from the GEO database, comprising 161 and 253 cases separately. Among these, 118 upregulated genes and 694 downregulated genes were identified. The upregulated DEGs were mainly involved in positive regulation of transcription from RNA polymerase II promoter, positive regulation of cartilage development, and response to wounding. The downregulated DEGs were enriched in chemical synaptic transmission, neurotransmitter secretion, and learning. By combining the results of PPI and miRNA-target network, 8 genes and 2 hub miRNAs were identified, including YWHAZ, DLG4, AGAP2, EGFR, TGFBR3, PSD3, RDX, BRWD1, and hsa-miR-106b-5p and hsa-miR-93-5p. These target genes are highly enriched in various key pathways, such as amyloid-beta formation, regulation of cardiocyte differentiation, and actin cytoskeleton reorganization.

CONCLUSIONS: In this study, YWHAZ, DLG4, AGAP2, EGFR, TGFBR3, PSD3, RDX, and BRWD1 were identified as candidate genes for future molecular studies in AD, which is expected to improve our understanding of its cause and potential molecular mechanisms. Nuclear genes, DEGs, and related networks identified by integrated bioinformatics analysis may serve as diagnostic and therapeutic targets for AD.

Keywords: Alzheimer Disease, Gene Expression Profiling, Hippocampus, Cell Nucleus, Cluster Analysis, Gene Expression Regulation, gene ontology, Gene Regulatory Networks, Neurotransmitter Agents, Protein Interaction Maps