Meta-Analysis of Gene Expression and Identification of Biological Regulatory Mechanisms in Alzheimer's Disease

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.

Perinuclear Lamin A and Nucleoplasmic Lamin B2 Characterize Two Types of Hippocampal Neurons through Alzheimer’s Disease Progression

“…All these phenomena are linked to the aberrant cell cycle re-entry that aged neurons initiate [36]. Heterochromatin modifications, in turn, result in decreased rRNA synthesis and induce nucleolar stress, affecting ribosome number, protein transduction, and gene expression [37][38][39]. In the nervous system, Lamins A/C, B1, and B2 present different expression levels and are instrumental for embryonary development and postnatal survival [40].…”

Royal Jelly as an Intelligent Anti-Aging Agent—A Focus on Cognitive Aging and Alzheimer’s Disease: A Review

“…Similarly, a combination of RJ and floral pollens resulted in significant amelioration of depressive symptoms, along with improvement of problem-solving capacity in postmenopausal women [ 126 , 127 ]. On top of this, the literature showed that RJ has the potential to improve general mental health of healthy volunteers [ 197 ]. It also documents antidepressant effects of RJ in animal models of depression and anxiety [ 201 , 212 ].…”

“…RJ is reported to improve testosterone, dehydroepiandrosterone sulfate, and estradiol in healthy adults [ 197 , 198 ]. It is widely used to treat infertility because of its phytoestrogen content [ 87 , 199 ].…”

Metabolomic and transcriptomic signatures of prenatal excessive methionine support nature rather than nurture in schizophrenia pathogenesis

“…Strikingly, Serpin3a (the human analogue of Serpina3n) displays the highest fold-changes in the brains of schizophrenia patients (2-fold increase, P = 1.14E-13, FDR = 1.62E-10), and two-fold increase in autism ( P = 0.004154, FDR = 0.059) 48 . Serpina3 is also overexpressed in Alzheimer’s as it enhances amyloid beta fibrillization and accelerated plaque formation 49 , 50 .…”