Identification of novel biomarkers linking depressive disorder and Alzheimer's disease based on an integrative bioinformatics analysis

Previous reports revealed that a history of major depressive disorder (MDD) increased the risk of Alzheimer's disease (AD). The immune disorder is associated with MDD and AD pathophysiology. We aimed to identify differentially expressed immune-related genes (DEIRGs) that are involved in the pathogenesis of MDD and AD.

We downloaded mRNA expression profiles (GSE76826 and GSE5281) from the Gene Expression Omnibus (GEO) database. The R software was used to identify DEIRGs for the two diseases separately. Functional enrichment analysis and PPI network of DEIRGs were performed. Finally, the relationship between shared DEIRGs and immune infiltrates of AD and MDD were analyzed, respectively.

A total of 121 DEIRGs linking AD and MDD were identified. These genes were significantly enriched in immune-related pathways, such as the JAK-STAT signaling pathway, regulation of chemotaxis, chemotaxis, cytokine-cytokine receptor interaction, and primary immunodeficiency. Furthermore, three shared DEIRGs (IL1R1, CHGB, and NRG1) were identified. Correlation analysis between DEIRGs and immune cells revealed that IL1R1 and NRG1 had a negative or positive correlation with some immune cells both in AD and MDD.

Both DEIRGs and immune cell infiltrations play a vital role in the pathogenesis of AD and MDD. Our findings indicated that there are common genes and biological processes between MDD and AD, which provides a theoretical basis for the study of the comorbidity of MDD and AD.