Abstract
Alzheimer's disease (AD), also known as senile dementia, is a progressive neurodegenerative disease. The etiology and pathogenesis of AD have not yet been elucidated. We examined common differentially expressed genes (DEGs) from different AD tissue microarray datasets by meta-analysis and screened the AD-associated genes from the common DEGs using GCBI. Then we studied the gene expression network using the STRING database and identified the hub genes using Cytoscape. Furthermore, we analyzed the microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and single nucleotide polymorphisms (SNPs) associated with the AD-associated genes, and then identified feed-forward loops. Finally, we performed SNP analysis of the AD-associated genes. Our results identified 207 common DEGs, of which 57 have previously been reported to be associated with AD. The common DEG expression network identified eight hub genes, all of which were previously known to be associated with AD. Further study of the regulatory miRNAs associated with the AD-associated genes and other genes specific to neurodegenerative diseases revealed 65 AD-associated miRNAs. Analysis of the miRNA associated transcription factor-miRNA-gene-gene associated TF (mTF-miRNA-gene-gTF) network around the AD-associated genes revealed 131 feed-forward loops (FFLs). Among them, one important FFL was found between the gene SERPINA3, hsa-miR-27a, and the transcription factor MYC. Furthermore, SNP analysis of the AD-associated genes identified 173 SNPs, and also found a role in AD for miRNAs specific to other neurodegenerative diseases, including hsa-miR-34c, hsa-miR-212, hsa-miR-34a, and hsa-miR-7. The regulatory network constructed in this study describes the mechanism of cell regulation in AD, in which miRNAs and lncRNAs can be considered AD regulatory factors.
Highlights
Alzheimer’s disease (AD) is the most well-reported neurodegenerative disease, and seriously affects patients’ ability to perform daily activities
We found transcription factor associated with gene (gTF) for the hub genes Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), ribosomal protein S27a (RPS27A), Glial fibrillary acidic protein (GFAP), Beta-2 microglobulin (B2M), Clusterin (CLU), Eukaryotic elongation factor 2 (EEF2), Gap junction protein alpha 1 (GJA1), and Ceruloplasmin (CP)
Our study identified several single nucleotide polymorphism (SNP) associated with five other neurodegenerative disease-associated miRNAs involved in feed-forward loop (FFL) of the regulatory network
Summary
Alzheimer’s disease (AD) is the most well-reported neurodegenerative disease, and seriously affects patients’ ability to perform daily activities. Genome-wide association studies (GWAS) studies have revealed that some single nucleotide polymorphisms (SNPs) contribute to AD disease onset. These include common variants such as estrogen receptor 1 (ESR1), presenilin 1 (PSEN1), cholinergic receptor muscarinic 2 (CHRM2), cholinergic receptor muscarinic 3 (CHRM3), apolipoprotein E (APOE), apolipoprotein C1 (APOC1), and choline acetyltransferase (CHAT) (Zhou et al, 2014; Liu et al, 2016; Bagyinszky et al, 2018; Chee and Cumming, 2018; Li et al, 2018), and rare variants in genes such as eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3) (Wong et al, 2018). EIF2AK3 polymorphisms are related to a risk of delayed AD (Liu et al, 2013), their function in neurodegenerative diseases is not very clear
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