Transcriptomic and network analysis identifies shared pathways across Alzheimer's disease and vascular dementia.

Abstract

Alzheimer's disease (AD) and vascular dementia (VaD) are often accompanied, but there are no effective differential diagnosis and treatment for VaD. The search for common pathogenic targets or pathways connecting the two diseases is helpful to the drug development and treatment of the disease. In this study, we used gene expression array data from the GEO database to analyze common differentially expressed genes (DEGs) in the temporal cortex of patients with AD and VaD. AD and VaD shared 143 DEGs. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that the biological function of common DEGs was mainly related to chemical synaptic transmission, neuroactive ligand-receptor, and cytokine-cytokine receptor interaction pathway. The protein-protein interaction (PPI) analysis showed the interaction of down- and up-regulated DEGs. The mRNA expression levels of key proteins in neuroactive ligand-receptor and cytokine-cytokine receptor interaction pathway were verified in AD and VaD mice. The real-time quantitative polymerase chain reaction (RT-qPCR) test was used to detect the expression of DEGs. Data of RT-qPCR showed the mRNA level of γ-aminobutyric acid type B receptor subunit 1 (GABBR1) was decreased in both AD and VaD. In addition, the mRNA of interleukin-17 receptor A (IL-17RA), IL-17 and IL-18 were increased. In conclusion, the shared genes in AD and VaD were verified in our study. We identified the critical genes to offer a theoretical basis for understanding the linkage of AD and VaD, which provided potential drug targets against AD and VaD.