Diagnostic Models and Predictive Drugs Associated with Cuproptosis Hub Genes in Alzheimer's Disease

Overview

Journal Front Neurol

Specialty Neurology

Date 2023 Feb 13

PMID 36776574

Authors

Erdong Zhang

Fengqiu Dai

Tingting Chen

Shanhui Liu

Chaolun Xiao

Xiangchun Shen

Affiliations

Soon will be listed here.

Abstract

Alzheimer's disease (AD) is a chronic neurodegenerative disease, and its underlying genes and treatments are unclear. Abnormalities in copper metabolism can prevent the clearance of β-amyloid peptides and promote the progression of AD pathogenesis. Therefore, the present study used a bioinformatics approach to perform an integrated analysis of the hub gene based on cuproptosis that can influence the diagnosis and treatment of AD. The gene expression profiles were obtained from the Gene Expression Omnibus database, including non-demented (ND) and AD samples. A total of 2,977 cuproptosis genes were retrieved from published articles. The seven hub genes associated with cuproptosis and AD were obtained from the differentially expressed genes and WGCNA in brain tissue from GSE33000. The GO analysis demonstrated that these genes were involved in phosphoribosyl pyrophosphate, lipid, and glucose metabolism. By stepwise regression and logistic regression analysis, we screened four of the seven cuproptosis genes to construct a diagnostic model for AD, which was validated by GES15222, GS48350, and GSE5281. In addition, immune cell infiltration of samples was investigated for correlation with these hub genes. We identified six drugs targeting these seven cuproptosis genes in DrugBank. Hence, these cuproptosis gene signatures may be an important prognostic indicator for AD and may offer new insights into treatment options.

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References

Tolles J, Meurer W . Logistic Regression: Relating Patient Characteristics to Outcomes. JAMA. 2016; 316(5):533-4. DOI: 10.1001/jama.2016.7653. View

Cao D, Lu H, Lewis T, Li L . Intake of sucrose-sweetened water induces insulin resistance and exacerbates memory deficits and amyloidosis in a transgenic mouse model of Alzheimer disease. J Biol Chem. 2007; 282(50):36275-82. DOI: 10.1074/jbc.M703561200. View

Blasko I, Veerhuis R, Stampfer-Kountchev M, Saurwein-Teissl M, Eikelenboom P, Grubeck-Loebenstein B . Costimulatory effects of interferon-gamma and interleukin-1beta or tumor necrosis factor alpha on the synthesis of Abeta1-40 and Abeta1-42 by human astrocytes. Neurobiol Dis. 2000; 7(6 Pt B):682-9. DOI: 10.1006/nbdi.2000.0321. View

Imming P, Sinning C, Meyer A . Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006; 5(10):821-34. DOI: 10.1038/nrd2132. View

Lee J, Lee B, Park C . Photo-induced inhibition of Alzheimer's β-amyloid aggregation in vitro by rose bengal. Biomaterials. 2014; 38:43-9. DOI: 10.1016/j.biomaterials.2014.10.058. View

Zhu M, Wang X, Sun L, Schultzberg M, Hjorth E . Can inflammation be resolved in Alzheimer's disease?. Ther Adv Neurol Disord. 2018; 11:1756286418791107. PMC: 6088473. DOI: 10.1177/1756286418791107. View

Newcombe E, Camats-Perna J, Silva M, Valmas N, Jong Huat T, Medeiros R . Inflammation: the link between comorbidities, genetics, and Alzheimer's disease. J Neuroinflammation. 2018; 15(1):276. PMC: 6154824. DOI: 10.1186/s12974-018-1313-3. View

Strosznajder A, Wojtowicz S, Jezyna M, Sun G, Strosznajder J . Recent Insights on the Role of PPAR-β/δ in Neuroinflammation and Neurodegeneration, and Its Potential Target for Therapy. Neuromolecular Med. 2020; 23(1):86-98. PMC: 7929960. DOI: 10.1007/s12017-020-08629-9. View

Scheiber I, Mercer J, Dringen R . Metabolism and functions of copper in brain. Prog Neurobiol. 2014; 116:33-57. DOI: 10.1016/j.pneurobio.2014.01.002. View

10.

Tana C, Ticinesi A, Prati B, Nouvenne A, Meschi T . Uric Acid and Cognitive Function in Older Individuals. Nutrients. 2018; 10(8). PMC: 6115794. DOI: 10.3390/nu10080975. View

11.

Semba R . Perspective: The Potential Role of Circulating Lysophosphatidylcholine in Neuroprotection against Alzheimer Disease. Adv Nutr. 2020; 11(4):760-772. PMC: 7360459. DOI: 10.1093/advances/nmaa024. View

12.

Ayton S, Lei P, Bush A . Metallostasis in Alzheimer's disease. Free Radic Biol Med. 2012; 62:76-89. DOI: 10.1016/j.freeradbiomed.2012.10.558. View

13.

Paolo G, Kim T . Linking lipids to Alzheimer's disease: cholesterol and beyond. Nat Rev Neurosci. 2011; 12(5):284-96. PMC: 3321383. DOI: 10.1038/nrn3012. View

14.

Peters-Golden M, Brock T . 5-lipoxygenase and FLAP. Prostaglandins Leukot Essent Fatty Acids. 2003; 69(2-3):99-109. DOI: 10.1016/s0952-3278(03)00070-x. View

15.

Zenaro E, Pietronigro E, Della Bianca V, Piacentino G, Marongiu L, Budui S . Neutrophils promote Alzheimer's disease-like pathology and cognitive decline via LFA-1 integrin. Nat Med. 2015; 21(8):880-6. DOI: 10.1038/nm.3913. View

16.

Sandin L, Bergkvist L, Nath S, Kielkopf C, Janefjord C, Helmfors L . Beneficial effects of increased lysozyme levels in Alzheimer's disease modelled in Drosophila melanogaster. FEBS J. 2016; 283(19):3508-3522. PMC: 5132093. DOI: 10.1111/febs.13830. View

17.

Chai K, Zhang X, Chen S, Gu H, Tang H, Cao P . Application of weighted co-expression network analysis and machine learning to identify the pathological mechanism of Alzheimer's disease. Front Aging Neurosci. 2022; 14:837770. PMC: 9326231. DOI: 10.3389/fnagi.2022.837770. View

18.

Barnham K, Masters C, Bush A . Neurodegenerative diseases and oxidative stress. Nat Rev Drug Discov. 2004; 3(3):205-14. DOI: 10.1038/nrd1330. View

19.

Newman A, Liu C, Green M, Gentles A, Feng W, Xu Y . Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015; 12(5):453-7. PMC: 4739640. DOI: 10.1038/nmeth.3337. View

20.

Xia L, Pang Y, Li J, Wu B, Du Y, Chen Y . Dihydroartemisinin Induces O-GlcNAcylation and Improves Cognitive Function in a Mouse Model of Tauopathy. J Alzheimers Dis. 2021; 84(1):239-248. DOI: 10.3233/JAD-210643. View