Identification of vascular dementia and Alzheimer's disease hub genes expressed in the frontal lobe and temporal cortex by weighted co-expression network analysis and construction of a protein–protein interaction

Abstract

Background: It is difficult to distinguish cognitive decline due to AD from that sustained by cerebrovascular disease in view of the great overlap. It is uncertain in the molecular biological pathway behind AD and VaD. Objective: Our study aimed to explore the hub molecules and their associations with each other to identify potential biomarkers and therapeutic targets for the AD and VaD. Methods: We screened the differentially expressed genes of AD and VaD, used weighted gene co-expression network analysis and then constructed a VaD–AD-specific protein–protein interaction network with functional annotation to their related metabolic pathways. Finally, we performed a ROC curve analysis of hub proteins to get an idea about their diagnostic value. Results: In the frontal lobe and temporal cortex, hub genes were identified. With regard to VaD, there were only three hub genes which encoded the neuropeptides, SST, NMU and TAC1. The AUC of these genes were 0.804, 0.768 and 0.779, respectively. One signature was established for these three hub genes with AUC of 0.990. For the identification of AD and VaD, all hub genes were receptors. These genes included SH3GL2, PROK2, TAC3, HTR2A, MET, TF, PTH2R CNR1, CHRM4, PTPN3 and CRH. The AUC of these genes were 0.853, 0.859, 0.796, 0.775, 0.706, 0.677, 0.696, 0.668 and 0.652, respectively. The other signature was built for eleven hub genes with AUC of 0.990. Conclusion: In the frontal lobe and temporal cortex regions, hub genes are used as diagnostic markers, which may provide insight into personalized potential biomarkers and therapeutic targets for patients with VaD and AD.