Shared Peripheral Blood Biomarkers for Alzheimer's Disease, Major Depressive Disorder, and Type 2 Diabetes and Cognitive Risk Factor Analysis

Overview

Journal Heliyon

Specialty Social Sciences

Date 2023 Mar 30

PMID 36994393

Authors

Yu Zhang

Rulin Geng

Miao Liu

Shengfeng Deng

Jingwen Ding

Hongfei Zhong

Qiuyun Tu

Affiliations

Soon will be listed here.

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, , , , , , , and . 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.

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References

Mega J, Stitziel N, Smith J, Chasman D, Caulfield M, Devlin J . Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials. Lancet. 2015; 385(9984):2264-2271. PMC: 4608367. DOI: 10.1016/S0140-6736(14)61730-X. View

Petersen J, Waldorff F, Siersma V, Phung T, Bebe A, Waldemar G . Major Depressive Symptoms Increase 3-Year Mortality Rate in Patients with Mild Dementia. Int J Alzheimers Dis. 2017; 2017:7482094. PMC: 5397625. DOI: 10.1155/2017/7482094. View

Zhang C, Kuang M, Li M, Feng L, Zhang K, Cheng S . SMC4, which is essentially involved in lung development, is associated with lung adenocarcinoma progression. Sci Rep. 2016; 6:34508. PMC: 5043270. DOI: 10.1038/srep34508. View

Kaup A, Byers A, Falvey C, Simonsick E, Satterfield S, Ayonayon H . Trajectories of Depressive Symptoms in Older Adults and Risk of Dementia. JAMA Psychiatry. 2016; 73(5):525-31. PMC: 5082978. DOI: 10.1001/jamapsychiatry.2016.0004. View

Konishi Y, Stegmuller J, Matsuda T, Bonni S, Bonni A . Cdh1-APC controls axonal growth and patterning in the mammalian brain. Science. 2004; 303(5660):1026-30. DOI: 10.1126/science.1093712. View

Maurer K, Hoyer S . Alois Alzheimer revisited: differences in origin of the disease carrying his name. J Neural Transm (Vienna). 2006; 113(11):1645-58. DOI: 10.1007/s00702-006-0592-5. View

Lin E, Von Korff M, Alonso J, Angermeyer M, Anthony J, Bromet E . Mental disorders among persons with diabetes--results from the World Mental Health Surveys. J Psychosom Res. 2008; 65(6):571-80. PMC: 3672403. DOI: 10.1016/j.jpsychores.2008.06.007. View

Ito J, Hashimoto T, Nakamura S, Aita Y, Yamazaki T, Schlegel W . Splicing transitions of the anchoring protein ENH during striated muscle development. Biochem Biophys Res Commun. 2012; 421(2):232-8. DOI: 10.1016/j.bbrc.2012.03.142. View

Huseby C, Hoffman C, Cooper G, Cocuron J, Alonso A, Thomas S . Quantification of Tau Protein Lysine Methylation in Aging and Alzheimer's Disease. J Alzheimers Dis. 2019; 71(3):979-991. PMC: 6844542. DOI: 10.3233/JAD-190604. View

10.

Wang R, Reddy P . Role of Glutamate and NMDA Receptors in Alzheimer's Disease. J Alzheimers Dis. 2016; 57(4):1041-1048. PMC: 5791143. DOI: 10.3233/JAD-160763. View

11.

Reus G, Dos Santos M, Strassi A, Abelaira H, Ceretta L, Quevedo J . Pathophysiological mechanisms involved in the relationship between diabetes and major depressive disorder. Life Sci. 2017; 183:78-82. DOI: 10.1016/j.lfs.2017.06.025. View

12.

Kapellos T, Bonaguro L, Gemund I, Reusch N, Saglam A, Hinkley E . Human Monocyte Subsets and Phenotypes in Major Chronic Inflammatory Diseases. Front Immunol. 2019; 10:2035. PMC: 6728754. DOI: 10.3389/fimmu.2019.02035. View

13.

Valente T, Gella A, Fernandez-Busquets X, Unzeta M, Durany N . Immunohistochemical analysis of human brain suggests pathological synergism of Alzheimer's disease and diabetes mellitus. Neurobiol Dis. 2009; 37(1):67-76. DOI: 10.1016/j.nbd.2009.09.008. View

14.

Petersen M, Shulman G . Mechanisms of Insulin Action and Insulin Resistance. Physiol Rev. 2018; 98(4):2133-2223. PMC: 6170977. DOI: 10.1152/physrev.00063.2017. View

15.

Wu T, Hu E, Xu S, Chen M, Guo P, Dai Z . clusterProfiler 4.0: A universal enrichment tool for interpreting omics data. Innovation (Camb). 2021; 2(3):100141. PMC: 8454663. DOI: 10.1016/j.xinn.2021.100141. View

16.

Yan Y, Li T, Li Z, He M, Wang D, Xu Y . Metformin Suppresses the Progress of Diabetes-Accelerated Atherosclerosis by Inhibition of Vascular Smooth Muscle Cell Migration Through AMPK-Pdlim5 Pathway. Front Cardiovasc Med. 2021; 8:690627. PMC: 8342753. DOI: 10.3389/fcvm.2021.690627. View

17.

Kazemi-Sefat G, Keramatipour M, Talebi S, Kavousi K, Sajed R, Kazemi-Sefat N . The importance of CDC27 in cancer: molecular pathology and clinical aspects. Cancer Cell Int. 2021; 21(1):160. PMC: 7941923. DOI: 10.1186/s12935-021-01860-9. View

18.

Li N, Zhao C, Wang Y, Yuan X . The transcription factor Cux1 regulates dendritic morphology of cortical pyramidal neurons. PLoS One. 2010; 5(5):e10596. PMC: 2868054. DOI: 10.1371/journal.pone.0010596. View

19.

Soria Lopez J, Gonzalez H, Leger G . Alzheimer's disease. Handb Clin Neurol. 2019; 167:231-255. DOI: 10.1016/B978-0-12-804766-8.00013-3. View

20.

Pearson E, Starkey B, Powell R, Gribble F, Clark P, Hattersley A . Genetic cause of hyperglycaemia and response to treatment in diabetes. Lancet. 2003; 362(9392):1275-81. DOI: 10.1016/S0140-6736(03)14571-0. View