title: In silico analyses for molecular genetic mechanism and candidate genes in patients with Alzheimer's disease.
abstract: This study aimed to identify candidate genes and explore the molecular pathogenesis of Alzheimer's disease (AD). Exon microarray data composed by of three human entorhinal cortex samples of AD patients and three non-demented controls (NDC) were analyzed, then expression profile data were preprocessed with the Oligo package and differentially expressed genes (DEGs) were identified by limma package in R/Bioconductor. In addition, protein-protein interaction (PPI) network was predicted and constructed using the STRING database. Finally, gene ontology (GO)-biological processes (BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enriched by DEGs were recognized. A total of 124 up-regulated and 218 down-regulated genes were identified. TGF-beta-activated kinase 1/MAP3K7 binding protein 2 (TAB 2) and chromogranin B (secretogranin 1) (CHGB) were the significantly up- and down-regulated genes, respectively. In addition, DEGs of DnaJ (Hsp40) homolog, subfamily B, member 1 (DNAJB1) and heat shock 70 kDa protein 1A (HSPA1A) were in the up-regulated network, while synaptophysin (SYP) and somatostatin (SST) were in the down-regulated network. Furthermore, the up-regulated genes were enriched in GO-BP terms of protein stimulus, unfolding and organic substance, etc., and pathways of ECM-receptor interaction, etc. The down-regulated genes were mainly associated with nerve-related transmission and neuroactive substances transportation. Protein folding abnormality and altered synaptic transmission could have a synergistic effect on the pathomechanism of AD. DEGs including DNAJB1 and HSPA1A may be involved in both the processes, while CHGB, SYP and SST may be important for the regulation of synaptic transmission to contribute to the progress and development of AD.
authors.affiliation: Department of Neurology, China-Japan Union Hospital of Jilin University, No 126 Xintai Street, Changchun, 130000, Jilin, China.
authors.forename: Lu-Mei
authors.initials: LM
authors.lastname: Chi
authors.affiliation: Cancer Center, First Affiliated Hospital, Jilin University, Changchun, 130061, Jilin, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurology, China-Japan Union Hospital of Jilin University, No 126 Xintai Street, Changchun, 130000, Jilin, China. nanguangdhhd@hotmail.com.
authors.forename: Guang-Xian
authors.initials: GX
authors.lastname: Nan
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D066298:In Vitro Techniques; D020411:Oligonucleotide Array Sequence Analysis; D059467:Transcriptome
keywords: Alzheimer’s disease; Differentially expressed genes; Exon microarray data; Functional enrichment analysis; Protein–protein interaction network