Transcriptomic analysis identifies shared biological foundations between ischemic stroke and Alzheimer’s disease

Abstract

AimAlzheimer’s disease (AD) and ischemic stroke (IS), two major neurological diseases, are suggested to be associated in clinical and pathophysiological levels. Previous studies have provided some insights into the possible genetic mechanisms behind the correlation between AD and IS, but this issue is still not clear. We implemented transcriptomic analysis to detect common hub genes and pathways to help promote the understanding of this issue.Materials and methodsFour gene expression profiling datasets (GSE16561, GSE58294, GSE63060, and GSE63061) of peripheral whole blood, which contain 108 IS samples, 284 AD samples, and 285 matched controls, were employed to detect differentially expressed genes (DEGs) for AD and IS, which were further analyzed for shared biological pathways, candidate drugs, and transcription factors. Protein-protein interaction (PPI) network and drug-target interaction analysis were applied to identify hub genes and drug targets, respectively. Result verification was done with other independent datasets (GSE37587, GSE46480, and GSE140829). The difference in proportions of various immune cells in the peripheral blood of AD and IS patients were evaluated using CIBERSORT.ResultsWe identified 74 DEGs and 18 biological processes with statistical significance shared by AD and IS, 9 of which were immune-related pathways. Five hub genes scored high in the topological analysis of the PPI network, and we also found eight drug target genes and candidate drugs which were associated with AD and IS. As for immunological changes, an increase in the proportion of M0 macrophages was found in the peripheral circulation of both AD and IS patients, and SOD1 expression was significantly correlated with this change.ConclusionCollectively, the common DEGs and shared pathways found in this study suggest a potential shared etiology between AD and IS, behind which immune system, particularly the M0 macrophage elevation, might have important roles. While, the shared hub genes, potential therapeutic gene targets and drugs reported in this study provide promising treatment strategies for AD and IS.

A review and analysis of key biomarkers in Alzheimer’s disease

“…Furthermore, protein-drug interaction analysis revealed that PDE9A interacts with drugs such as caffeine, γ-glutamyl glycine, and 3-isobutyl-1-methyl-7H-xanthine. Through the PPI and network topology analysis for the common DEGs, Liu W. et al (2022) identified hub genes RPS3, RPS15, PSMB6, MRPL17, and MRPL24 of AD and IS.…”

Competing endogenous RNA network analysis of the molecular mechanisms of ischemic stroke

“…The data were quantile normalized, and the differential expressed miRNAs (DEmiRNAs), mRNAs (DEmRNAs), and lncRNAs (DElncRNAs) between the IS and control samples were identified using R's limma package (v3.52.0) [19]. The P < 0.05, |log 2-fold change (FC)| > 0.5 were selected as cut-off criteria in identifying DEmRNAs and DEmiRNAs by previously reported methods [10,21,[28][29][30], and |log 2-fold change (FC)| > 1 was selected to identify DElncRNA [31,32]. Thereafter, volcano plots of DEmiRNAs, DElncRNAs, and DEmRNAs were generated using the ggplot2 package (v3.3.6) [33].…”

Cardiovascular Disease and Alzheimer's Disease: The Heart–Brain Axis

“… 116 Recently, Liu and coworkers identified 74 differentially expressed genes and largely immune‐related pathways shared in AD pathology and ischemic stroke. 117 …”