Shared peripheral blood biomarkers for Alzheimer’s disease, major depressive disorder, and type 2 diabetes and cognitive risk factor analysis
Yu Zhang, Rulin Geng, Miao Liu, Shengfeng Deng, Jingwen Ding, Hongfei Zhong, Qiuyun Tu
Abstract
Background Alzheimer's disease (AD), type 2 diabetes mellitus (T2DM), and Major Depressive Disorder (MDD) have a higher incidence rate in modern society. Although increasing evidence supports close associations between the three, the mechanisms underlying their interrelationships remain elucidated. Objective The primary purpose is to explore the shared pathogenesis and the potential peripheral blood biomarkers for AD, MDD, and T2DM. Methods We downloaded the microarray data of AD, MDD, and T2DM from the Gene Expression Omnibus database and constructed co-expression networks by Weighted Gene Co-Expression Network Analysis to identify differentially expressed genes. We took the intersection of differentially expressed genes to obtain co-DEGs. Then, we performed GO and KEGG enrichment analysis on the common genes in the AD, MDD, and T2DM-related modules. Next, we utilized the STRING database to find the hub genes in the protein-protein interaction network. ROC curves were constructed for co-DEGs to obtain the most diagnostic valuable genes and to make drug predictions against the target genes. Finally, we conducted a present condition survey to verify the correlation between T2DM, MDD and AD. Results Our findings indicated 127 diff co-DEGs, 19 upregulated co-DEGs, and 25 down-regulated co-DEGs. Functional enrichment analysis showed co-DEGs were mainly enriched in signaling pathways such as metabolic diseases and some neurodegeneration. Protein-protein interaction network construction identified hub genes in AD, MDD and T2DM shared genes. We identified seven hub genes of co-DEGs, namely, SMC4 , CDC27 , HNF1A , RHOD , CUX1 , PDLIM5 , and TTR . The current survey results suggest a correlation between T2DM, MDD and dementia. Moreover, logistic regression analysis showed that T2DM and depression increased the risk of dementia. Conclusion Our work identified common pathogenesis of AD, T2DM, and MDD. These shared pathways might provide novel ideas for further mechanistic studies and hub genes that may serve as novel therapeutic targets for diagnosing and treating.