Integrated Bioinformatic Analysis and Validation Identifies Immune Microenvironment-Related Potential Biomarkers in...

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, accompanied by cognitive and memory impairment, accounting for about 60% - 80% of dementia types. The pathogenesis of AD has not been clarified, and there is no effective therapy to prevent or treat AD. In this study, we aimed to identify the potential biomarkers involved in the brain immune microenvironment in AD.

AD datasets from GEO database were obtained to identify the differentially expressed disease-related genes (DEDRGs) in AD through weighted gene co-expression network analysis (WGCNA) and differential expression analysis. Functional Enrichment analysis was performed to explore the potential biological function of DEDRGs. The hub DEDRGs were identified through the protein-protein interaction (PPI) network. Furthermore, the CIBERSORT algorithm was employed to bulk gene expression profiles of AD to depict the immune microenvironment characteristics in AD. Pearson's correlation analysis was utilized to depict the correlation between each of immune cells and hub DEDRGs.

A total of 27 DEDRGs were identified through WGCNA and differential expression analysis. Functional enrichment analysis of 27 DEDRGs indicated that chemokine signaling pathway was the most significantly enriched KEGG pathway, response to biotic stimulus was the most significantly enriched GO term, and most of DEDRGs were enriched into urinary system cancer in DO analysis. 6 hub DEDRGs, ANGPT1, CCL2, CD44, CXCR4, GJA1 and VCAM1, were screened through PPI network and all of them were up-regulated in AD. Immune infiltration analysis revealed that there were higher infiltration levels of T cells CD4 memory activated, T cells gamma delta, NK cells resting and macrophages M0, and lower infiltration level of NK cell activated in AD, and macrophages M2 owned the highest positively association with VCAM1 and CXCR4, but VCAM1 was statistically and negatively correlated to T cells CD8.

Our study identified 6 hub DEDRGs, ANGPT1, CCL2, CD44, CXCR4, GJA1 and VCAM1, were statistically associated with immune infiltrating cells, and were significantly related to the pathological development of AD, which may provide a theoretical basis for developing potential biomarkers and implementing effective therapies against AD.