结构生物信息学知识库

Background: Alzheimer disease (AD) is a common neurodegenerative disorder with distinct pathological features, with agingconsidered the greatest risk factor. We explored how aging contributes to increased AD risk, and determined concurrent andcoordinate changes (including genetic and phenotypic modifications) commonly exhibited in both normal aging and AD.

Methods: UsingtheGeneExpressionOmnibus(GEO)database,wecollected1healthyaging-relatedand3AD-relateddatasetsofthe hippocampal region. The normal aging dataset was divided into 3 age groups: young (20–40 years old), middle-aged (40–60years old), and elderly (>60 years old). These datasets were used to analyze the differentially expressed genes (DEGs). The GeneOntology (GO) terms, pathways, and function network analysis of these DEGs were analyzed.Results: One thousand two hundred ninety-one DEGs were found to be shared in the natural aging groups and AD patients.Among the shared DEGs, ATP6V1E1, GNG3, NDUFV2, GOT1, USP14, and NAV2 have been previously found in both normal agingindividuals and AD patients. Furthermore, using Java Enrichment of Pathways Extended to Topology (JEPETTO) analysis based onKyotoEncyclopediaofGenesandGenomes(KEGG)database,wedeterminedthatchangesinaging-relatedKEGGannotationsmaycontribute to the aging-dependence of AD risk. Interestingly, NRXN3, the second most commonly deregulated gene identified in thepresent study, is known to carry a mutation in AD patients. According to functional network analysis, NRXN3 plays a critical role insynaptic functions involved in the cognitive decline associated with normal aging and AD.

Conclusion: Our results indicate that the low expression of aging-related NRXN3 may increase AD risk, though the potentialmechanism requires further clarification.Abbreviations: Ab = amyloid beta, AD = Alzheimer disease, DEGs = differentially expressed genes, FDR = false discovery rate,GEO = Gene Expression Omnibus, JEPETTO = Java Enrichment of Pathways Extended to Topology, KEGG = Kyoto Encyclopediaof Genes and Genomes, MCODE = molecular complex detection, NCBI = National Center for Biotechnology Information, NLGN =neuroligin, NRXN = neurexin, PTPRT = receptor-type tyrosine-protein phosphatase T, RMA = robust multichip average, SAM =significance analysis of microarrays, SNPs = single nucleotide polymorphisms.