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

doi:10.1016/j.heliyon.2023.e14653

Shared peripheral blood biomarkers for Alzheimer's disease, major depressive disorder, and type 2 diabetes and cognitive risk factor analysis

Heliyon. 2023 Mar 17;9(3):e14653. doi: 10.1016/j.heliyon.2023.e14653. eCollection 2023 Mar.

Authors

Yu Zhang¹, Rulin Geng¹, Miao Liu¹, Shengfeng Deng¹, Jingwen Ding¹, Hongfei Zhong¹, Qiuyun Tu¹

Affiliation

¹ Department of Geriatrics, The Fifth Affiliated Hospital Sun Yat-Sen University, Zhuhai 519000, China.

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.

Keywords: Alzheimer's disease; Bioinformatics analysis; Functional enrichment analysis; Major depressive disorder; Protein-protein interaction network; Type 2 diabetes.