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

Abstract

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.

Keywords:

• Alzheimer’s disease
• vascular dementia
• weighted gene co-expression network analysis
• LASSO
• WGCNA

Data Sharing Statement

The raw analyses from this study and codes can be obtained from the corresponding author upon reasonable request.

Author Contributions

FKZ, DYC, GYC, DHZ and XFL conceived and designed the study. All authors contributed to data analysis, drafting or revising the article, have agreed on the journal to which the article will be submitted, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that this research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.