Abed Samin, Ebrahimi Amir, Fattahi Fatemeh, Shekari-Khaniani Mahmoud, Mansoori Derakhshan Sima
Department of Genetics, Tabriz University of Medical Sciences, Tabriz, Iran.
Mol Neurobiol. 2025 Apr 28. doi: 10.1007/s12035-025-04970-x.
Despite recent advancements, the development of an efficient and non-invasive early detection approach for Alzheimer's disease (AD) remains unresolved. The specificity of a diagnostic biomarker is contingent upon its foundation in the molecular basis of the diseases. Immune system dysfunction has a significant role in the genesis and progression of AِِD; thus, it should be included into the formulation of novel treatment and diagnostic strategies. A screening step was conducted through the analysis of a microarray dataset to identify differentially expressed genes (DEGs) and co-expression patterns using weighted gene co-expression network analysis. Subsequently, common genes were discovered and subjected to functional enrichment analysis. Subsequently, during the validation phase, the expression and diagnostic capabilities of candidate genes were evaluated in a group of 50 AD patients. Initially, 269 DEGs were found in the blood of AD patients. Analyzing the co-expression patterns revealed 18 distinct topological modules, with the module exhibiting the highest correlation (blue) selected for further study. A compilation of immune-related genes was extracted from the Immunology Database and Analysis Portal (ImmPort) and cross-referenced with DEGs and genes inside the blue module, as the blue module was found to primarily govern immune response. The anomalous expression of three potential genes-specifically IL17C, TEK, and CCL4-was confirmed in the blood of AD patients by RT-PCR. A biomarker panel consisting of these genes attained an accuracy of 80.2%. The proposed biomarker in this study is based on the immunological response observed in AD and demonstrates high precision in identifying patients.
尽管近年来取得了进展,但针对阿尔茨海默病(AD)的高效、非侵入性早期检测方法仍未得到解决。诊断生物标志物的特异性取决于其在疾病分子基础上的依据。免疫系统功能障碍在AD的发生和发展中起着重要作用;因此,应将其纳入新的治疗和诊断策略的制定中。通过对微阵列数据集进行分析,利用加权基因共表达网络分析来识别差异表达基因(DEGs)和共表达模式,从而进行筛选步骤。随后,发现了共同基因并对其进行功能富集分析。随后,在验证阶段,在一组50名AD患者中评估候选基因的表达和诊断能力。最初,在AD患者的血液中发现了269个DEGs。对共表达模式的分析揭示了18个不同的拓扑模块,选择相关性最高的模块(蓝色)进行进一步研究。从免疫学数据库和分析门户(ImmPort)中提取了免疫相关基因的汇编,并与DEGs以及蓝色模块内的基因进行交叉参考,因为发现蓝色模块主要控制免疫反应。通过RT-PCR在AD患者的血液中证实了三种潜在基因——特别是IL17C、TEK和CCL4——的异常表达。由这些基因组成的生物标志物组的准确率达到了80.2%。本研究中提出的生物标志物基于在AD中观察到的免疫反应,在识别患者方面表现出高精度。