Identification of Genetic Markers and Immune Infiltration Characteristics of Alzheimer’s Disease Through Weighted Gene Co-expression Network Analysis

Abstract Background: Alzheimer disease (AD) is a long-term progressive neurodegeneration disease. Studies have shown that accumulation of epigenetic changes promotes the formation of gene mutations thereby inducing the pathogenesis of Alzheimer disease. Currently, the molecular mechanisms of alzheimer disease are not well defined. This calls for identification of genetic markers of alzheimer disease which can be leveraged to design effective drugs. Method: In this study, we aimed to determine the modules and hub genes that contribute to the development of alzheimer disease through weighted gene co-expression network analysis (WGCNA). The genes in the module were enriched and analyzed by GO / KEGG, and the protein-protein interaction（PPI） network was constructed. In addition, WGCNA topology analysis was carried out to construct a gene network, from which five hub genes were identified. Logistic regression analysis and Receiver operating characteristics (ROC) was performed to explore the clinical value of genes in diagnosis of Alzheimer. The genes in the core module are intersected with the hub genes, and four intersecting genes were selected, which were ATP2A2, ATP6V1D, CAP2 and SYNJ1. The four genes were enriched by GSEA. Finally, immune infiltration analysis was performed.Results: The GO/KEGG analysis shows that the genes in the core module play a role in the differentiation and growth of nerve cells and neurotransmitter transmission.Gene set enrichment analysis (GSEA) about core genes demonstrated that the four genes were mainly enriched in immune infection pathways such as cholera infection and Helicobacter pylori infection and other metabolic pathways. In addition, immune infiltration characteristics were investigated and found that T cells regulatory (Tregs), neutrophils, plasma cells, mast cells activated, T cells cellular helper, T cells CD8, T cells CD4 memory resetting and macrophases M1 are core immune cells contributing to the progression of Alzheimer's disease. Conclusion: The results of enrichment analysis and immunoosmotic analysis showed that immune pathways and immune cells played an important role in the occurrence and development of alzheimer disease. The selected key genes are used as biomarkers related to the pathogenesis of alzheimer disease to further explore the pathways and cells.