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转录组学和网络分析确定了阿尔茨海默病和血管性痴呆的共同通路。

Transcriptomic and network analysis identifies shared pathways across Alzheimer's disease and vascular dementia.

作者信息

Zheng Cengceng, Zhao Yejing, Hu Chaoying, Zhang Li, Li Gengkuo, Yang Cuicui

机构信息

Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing 100053, PR China.

Department of Gerontology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100005, PR China.

出版信息

Brain Res. 2025 May 1;1854:149548. doi: 10.1016/j.brainres.2025.149548. Epub 2025 Mar 4.

Abstract

Alzheimer's disease (AD) and vascular dementia (VaD) are often accompanied, but there are no effective differential diagnosis and treatment for VaD. The search for common pathogenic targets or pathways connecting the two diseases is helpful to the drug development and treatment of the disease. In this study, we used gene expression array data from the GEO database to analyze common differentially expressed genes (DEGs) in the temporal cortex of patients with AD and VaD. AD and VaD shared 143 DEGs. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that the biological function of common DEGs was mainly related to chemical synaptic transmission, neuroactive ligand-receptor, and cytokine-cytokine receptor interaction pathway. The protein-protein interaction (PPI) analysis showed the interaction of down- and up-regulated DEGs. The mRNA expression levels of key proteins in neuroactive ligand-receptor and cytokine-cytokine receptor interaction pathway were verified in AD and VaD mice. The real-time quantitative polymerase chain reaction (RT-qPCR) test was used to detect the expression of DEGs. Data of RT-qPCR showed the mRNA level of γ-aminobutyric acid type B receptor subunit 1 (GABBR1) was decreased in both AD and VaD. In addition, the mRNA of interleukin-17 receptor A (IL-17RA), IL-17 and IL-18 were increased. In conclusion, the shared genes in AD and VaD were verified in our study. We identified the critical genes to offer a theoretical basis for understanding the linkage of AD and VaD, which provided potential drug targets against AD and VaD.

摘要

阿尔茨海默病(AD)和血管性痴呆(VaD)常相伴出现,但目前尚无针对VaD的有效鉴别诊断和治疗方法。寻找连接这两种疾病的共同致病靶点或通路,有助于疾病的药物研发和治疗。在本研究中,我们使用来自基因表达综合数据库(GEO数据库)的基因表达阵列数据,分析AD和VaD患者颞叶皮质中的共同差异表达基因(DEG)。AD和VaD共有143个DEG。基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路富集分析表明,共同DEG的生物学功能主要与化学突触传递、神经活性配体-受体以及细胞因子-细胞因子受体相互作用通路有关。蛋白质-蛋白质相互作用(PPI)分析显示了下调和上调DEG的相互作用。在AD和VaD小鼠中验证了神经活性配体-受体和细胞因子-细胞因子受体相互作用通路中关键蛋白的mRNA表达水平。采用实时定量聚合酶链反应(RT-qPCR)试验检测DEG的表达。RT-qPCR数据显示,γ-氨基丁酸B型受体亚基1(GABBR1)的mRNA水平在AD和VaD中均降低。此外,白细胞介素-17受体A(IL-17RA)、IL-17和IL-18的mRNA水平升高。总之,我们的研究验证了AD和VaD中的共享基因。我们鉴定出关键基因,为理解AD和VaD的联系提供了理论基础,为抗AD和VaD的潜在药物靶点提供了依据。

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