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

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.