Abstract
BackgroundAlzheimer’s disease (AD) is known to be caused by multiple factors, meanwhile the pathogenic mechanism and development of AD associate closely with genetic factors. Existing understanding of the molecular mechanisms underlying AD remains incomplete.MethodsGene expression data (GSE48350) derived from post-modern brain was extracted from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were derived from hippocampus and entorhinal cortex regions between AD patients and healthy controls and detected via Morpheus. Functional enrichment analyses, including Gene Ontology (GO) and pathway analyses of DEGs, were performed via Cytoscape and followed by the construction of protein-protein interaction (PPI) network. Hub proteins were screened using the criteria: nodes degree≥10 (for hippocampus tissues) and ≥ 8 (for entorhinal cortex tissues). Molecular Complex Detection (MCODE) was used to filtrate the important clusters. University of California Santa Cruz (UCSC) and the database of RNA-binding protein specificities (RBPDB) were employed to identify the RNA-binding proteins of the long non-coding RNA (lncRNA).Results251 & 74 genes were identified as DEGs, which consisted of 56 & 16 up-regulated genes and 195 & 58 down-regulated genes in hippocampus and entorhinal cortex, respectively. Biological analyses demonstrated that the biological processes and pathways related to memory, transmembrane transport, synaptic transmission, neuron survival, drug metabolism, ion homeostasis and signal transduction were enriched in these genes. 11 genes were identified as hub genes in hippocampus and entorhinal cortex, and 3 hub genes were identified as the novel candidates involved in the pathology of AD. Furthermore, 3 lncRNAs were filtrated, whose binding proteins were closely associated with AD.ConclusionsThrough GO enrichment analyses, pathway analyses and PPI analyses, we showed a comprehensive interpretation of the pathogenesis of AD at a systematic biology level, and 3 novel candidate genes and 3 lncRNAs were identified as novel and potential candidates participating in the pathology of AD. The results of this study could supply integrated insights for understanding the pathogenic mechanism underlying AD and potential novel therapeutic targets.
Highlights
Alzheimer’s disease (AD) is known to be caused by multiple factors, the pathogenic mechanism and development of AD associate closely with genetic factors
Identification of differentially expressed genes (DEGs) The gene expression profile and sample information of post-mortem brain tissue samples of AD patients and normal people of GSE48350 were obtained from National Center of Biotechnology Information-Gene Expression Omnibus (NCBI-GEO) and ArrayExpress database, respectively, which are free databases of microarray/gene profile and next-generation sequencing
Employing Morpheus software and using p < 0.05 and |log2FC| ≥ 1 (FC, fold change) as cut-off criterion, 251 genes (56 upregulated and 195 down-regulated genes) and 74 genes (16 up-regulated and 58 down-regulated genes) were identified as DEGs in the AD samples compared with the normal ones in the tissues of hippocampus and entorhinal cortex, respectively (Table 1 and Additional file 2: Table S2)
Summary
Alzheimer’s disease (AD) is known to be caused by multiple factors, the pathogenic mechanism and development of AD associate closely with genetic factors. It is well known that AD has complex multiple pathogenic factors, such as genetic factor, environmental factor, immunological factor, head injuries, depression, or hypertension [4,5,6,7,8]. Among these factors, genetic factors are estimated to attribute about 70% to the risk for AD [9]. Except for identifying mechanisms involved in the AD pathogenesis, comprehensive analyses of potential candidate genes could suggest novel potential strategies to predictive or diagnostic test for AD
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