Zhang Erdong, Dai Fengqiu, Chen Tingting, Liu Shanhui, Xiao Chaolun, Shen Xiangchun
State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou, China.
Key Laboratory of Optimal Utilization of Natural Medicinal Resources, Guizhou Medical University, Guiyang, Guizhou, China.
Front Neurol. 2023 Jan 26;13:1064639. doi: 10.3389/fneur.2022.1064639. eCollection 2022.
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.
阿尔茨海默病（AD）是一种慢性神经退行性疾病，其潜在基因和治疗方法尚不清楚。铜代谢异常会阻碍β-淀粉样肽的清除，并促进AD发病机制的进展。因此，本研究采用生物信息学方法，基于可影响AD诊断和治疗的铜死亡对关键基因进行综合分析。基因表达谱来自基因表达综合数据库，包括非痴呆（ND）和AD样本。从已发表的文章中检索到总共2977个铜死亡基因。从GSE33000脑组织中的差异表达基因和加权基因共表达网络分析（WGCNA）中获得了与铜死亡和AD相关的7个关键基因。基因本体（GO）分析表明，这些基因参与磷酸核糖焦磷酸、脂质和葡萄糖代谢。通过逐步回归和逻辑回归分析，我们从7个铜死亡基因中筛选出4个构建AD诊断模型，并通过GES15222、GS48350和GSE5281进行验证。此外，还研究了样本的免疫细胞浸润与这些关键基因的相关性。我们在药物银行（DrugBank）中确定了6种靶向这7个铜死亡基因的药物。因此，这些铜死亡基因特征可能是AD的一个重要预后指标，并可能为治疗选择提供新的见解。
