Gene Set Index Based on Different Modules May Help Differentiate the Mechanisms of Alzheimer’s Disease and Vascular Dementia

PURPOSE: Alzheimer’s disease (AD) and vascular dementia shared similar symptoms, the aim of the present study was to identify potential differences in the mechanisms underlying the two diseases. MATERIALS AND METHODS: The data set including AD, vascular dementia, and control samples was carried out gene differential expression analysis, weighted gene co-expression network analysis, functional enrichment, protein–protein interaction network construction, and least absolute shrinkage and selection operator analysis to reveal the differences in the mechanisms underlying the two diseases and potential diagnostic gene signature. RESULTS: We identified the gene modules related to AD or vascular dementia. Enrichment analysis of module genes and construction of a protein–protein interaction network suggested that the “brown” module may be involved in a chemokine pathway, the “blue” module may be involved in cortisol synthesis and secretion, and the “turquoise” module may be involved in cholinergic synapse transmission. The hub gene-based signature index may be a biomarker of AD and vascular dementia and may even differentiate the two diseases from each other with high area under curve. CONCLUSION: Our results identified not only core pathways involved in both AD and vascular disease, but also their potentially specific pathways. We proposed the hub gene-based signature index may be useful for diagnosing AD and vascular dementia.