Alterations in NFAT5 and ATP6V1E1 expression as potential diagnostic biomarkers in blood and brain for Alzheimer’s disease: A study of gene overlap

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research Pub Date : 2025-04-03 DOI:10.1016/j.brainres.2025.149599

Farnoosh Akbari , Roksana Soheilian , Samin Tavalaeian , Atefeh Zamani , Mohammad Mahdevar

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引用次数: 0

Abstract

Introduction

Alzheimer’s disease (AD), a prevalent cause of dementia, is characterized by amyloid plaques and tau tangles. It requires early diagnosis through the use of blood markers. This study examined changes in gene expression in blood and brain samples from patients with AD as potential diagnostic biomarkers.

Methods

The study utilized gene expression data from publicly available studies, including GSE4757, GSE5281, GSE28146, GSE48350, and GSE63060, to investigate expression changes in AD. Data integration and differential expression analysis were performed, and pathways related to candidate genes were identified using the Enrichr and BioPlents databases. Blood samples from 50 AD and controls were collected, followed by RNA extraction, cDNA synthesis, and qRT-PCR analysis using specific NFAT5 and ATP6V1E1 gene primers.

Results

We found 394 genes with increased expression and 759 with decreased expression in brain tissue. Upregulated genes were linked to TGF-B, BDNF, apoptosis, Hippo, P53, and IL-2 and IL-4 pathways. In contrast, downregulated genes were associated with pathways related to oxidative phosphorylation, PGC1-A, GABA, Alzheimer’s, and calcium. Blood expression data showed 1147 probes with increased expression and 1413 with significant decreases. We found 31 genes that were upregulated and 87 genes that were downregulated, consistent across both blood and brain samples. Among the overlapping genes, RT-qPCR results indicated that the expression levels of NFAT5 and ATP6V1E1 may have diagnostic potential in the blood samples of Alzheimer’s patients.

Conclusion

The study identified changes in gene expression related to Alzheimer’s in blood and brain samples. These changes affect pathways such as IL-2 and oxidative phosphorylation. Both in silico and ex vivo results revealed that the expression levels of NFAT5 and ATP6V1E1 in blood samples can serve as potential diagnostic biomarkers for Alzheimer’s patients.

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NFAT5和ATP6V1E1表达的改变作为阿尔茨海默病血液和大脑的潜在诊断生物标志物：基因重叠的研究

简介：阿尔茨海默病（AD）是一种常见的痴呆症病因，其特征是淀粉样斑块和tau蛋白缠结。它需要通过血液标记物进行早期诊断。这项研究检测了AD患者血液和大脑样本中基因表达的变化，作为潜在的诊断生物标志物。方法：利用公开研究的基因表达数据，包括GSE4757、GSE5281、GSE28146、GSE48350和GSE63060，研究AD的表达变化。进行数据整合和差异表达分析，并使用enrichment和BioPlents数据库确定候选基因相关的途径。采集50例AD患者和对照组的血样，进行RNA提取、cDNA合成，并使用特异性NFAT5和ATP6V1E1基因引物进行qRT-PCR分析。结果：在脑组织中发现394个基因表达升高，759个基因表达降低。上调的基因与TGF-B、BDNF、凋亡、Hippo、P53、IL-2和IL-4通路有关。相反，下调的基因与氧化磷酸化、PGC1-A、GABA、阿尔茨海默病和钙相关的途径相关。血液表达数据显示1147个探针表达增加，1413个探针表达显著降低。我们发现31个基因上调，87个基因下调，在血液和大脑样本中都是一致的。在重叠基因中，RT-qPCR结果提示NFAT5和ATP6V1E1的表达水平在阿尔茨海默病患者血液样本中可能具有诊断潜力。结论：该研究在血液和大脑样本中发现了与阿尔茨海默病相关的基因表达变化。这些变化会影响IL-2和氧化磷酸化等途径。体外实验结果表明，血液样本中NFAT5和ATP6V1E1的表达水平可以作为阿尔茨海默病患者的潜在诊断生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Brain Research 医学-神经科学

CiteScore

5.90

自引率

3.40%

发文量

268

审稿时长

47 days

期刊介绍： An international multidisciplinary journal devoted to fundamental research in the brain sciences. Brain Research publishes papers reporting interdisciplinary investigations of nervous system structure and function that are of general interest to the international community of neuroscientists. As is evident from the journals name, its scope is broad, ranging from cellular and molecular studies through systems neuroscience, cognition and disease. Invited reviews are also published; suggestions for and inquiries about potential reviews are welcomed. With the appearance of the final issue of the 2011 subscription, Vol. 67/1-2 (24 June 2011), Brain Research Reviews has ceased publication as a distinct journal separate from Brain Research. Review articles accepted for Brain Research are now published in that journal.