Our study investigates the molecular link between COVID‐19 and Alzheimer's disease (AD). We aim to elucidate the mechanisms by which COVID‐19 may influence the onset or progression of AD. Using bioinformatic tools, we analyzed gene expression datasets from the Gene Expression Omnibus (GEO) database, including GSE147507, GSE12685, and GSE26927. Intersection analysis was utilized to identify common differentially expressed genes (CDEGs) and their shared biological pathways. Consensus clustering was conducted to group AD patients based on gene expression, followed by an analysis of the immune microenvironment and variations in shared pathway activities between clusters. Additionally, we identified transcription factor‐binding sites shared by CDEGs and genes in the common pathway. The activity of the pathway and the expression levels of the CDEGs were validated using GSE164805 and GSE48350 datasets. Six CDEGs (MAL2, NECAB1, SH3GL2, EPB41L3, MEF2C, and NRGN) were identified, along with a downregulated pathway, the endocannabinoid (ECS) signaling pathway, common to both AD and COVID‐19. These CDEGs showed a significant correlation with ECS activity (p < 0.05) and immune functions. The ECS pathway was enriched in healthy individuals' brains and downregulated in AD patients. Validation using GSE164805 and GSE48350 datasets confirmed the differential expression of these genes in COVID‐19 and AD tissues. Our findings reveal a potential pathogenetic link between COVID‐19 and AD, mediated by CDEGs and the ECS pathway. However, further research and multicenter evidence are needed to translate these findings into clinical applications.

中文翻译：

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探索分子途径：通过内源性大麻素系统动力学阐明 COVID-19 与阿尔茨海默病之间的联系

我们的研究调查了 COVID-19 和阿尔茨海默病 (AD) 之间的分子联系。我们的目标是阐明 COVID-19 可能影响 AD 发病或进展的机制。使用生物信息学工具，我们分析了基因表达综合 (GEO) 数据库中的基因表达数据集，包括 GSE147507、GSE12685 和 GSE26927。利用交叉分析来识别常见的差异表达基因（CDEG）及其共享的生物学途径。根据基因表达对 AD 患者进行共识聚类，然后分析免疫微环境和聚类之间共享途径活动的变化。此外，我们还确定了 CDEG 和共同途径中基因共享的转录因子结合位点。使用 GSE164805 和 GSE48350 数据集验证了该途径的活性和 CDEG 的表达水平。鉴定出六种 CDEG（MAL2、NECAB1、SH3GL2、EPB41L3、MEF2C 和 NRGN），以及 AD 和 COVID-19 共有的下调途径，即内源性大麻素 (ECS) 信号途径。这些 CDEG 显示与 ECS 活动显着相关（p< 0.05) 和免疫功能。 ECS 通路在健康个体的大脑中富集，而在 AD 患者的大脑中表达下调。使用 GSE164805 和 GSE48350 数据集的验证证实了这些基因在 COVID-19 和 AD 组织中的差异表达。我们的研究结果揭示了 COVID-19 和 AD 之间的潜在致病联系，由 CDEG 和 ECS 途径介导。然而，需要进一步的研究和多中心证据才能将这些发现转化为临床应用。