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晚发性阿尔茨海默病患者外周血单个核细胞中BACE1 mRNA水平升高与miR-15a-5p和miR-19b-3p表达降低相关:实验结果与生物信息学分析

Elevated BACE1 mRNA Level is Associated with Lower miR-15a-5p and miR-19b-3p Expressions in Peripheral Blood Mononuclear Cells of Patients with Late-Onset Alzheimer's Disease: Wet Lab Results and Bioinformatics Analysis.

作者信息

Rasadi Arezoo, Talesh Sasani Soheila, Ajamian Farzam

机构信息

Department of Biology, Faculty of Basic Sciences, University of Guilan, Rasht, Iran.

出版信息

Mol Neurobiol. 2025 Jun 27. doi: 10.1007/s12035-025-05159-y.

DOI:10.1007/s12035-025-05159-y
PMID:40576757
Abstract

BACE1 promotes aggregation of β-amyloid in Alzheimer's patients' brains. MicroRNAs play roles in gene expression regulation. Furthermore, BACE1 is a target for microRNAs. There is a crosstalk between the peripheral and central immune systems in the etiology of Alzheimer's disease. This study investigates the alterations in expression of BACE1, along with miR-15a-5p and miR-19b-3p genes, in peripheral blood mononuclear cells (PBMCs) of late-onset Alzheimer's disease (LOAD) patients. The levels of BACE1 mRNA, miR-15a-5p, and miR-19b-3p were measured in PBMCs using a real-time quantitative PCR method. Cytoscape software was used to identify the putative target genes of these microRNAs. Significant increase in BACE1 levels (mean ± SD: 2.076 ± 0.5308), and decrease in both miR-15a-5p and miR-19b-3p expressions (0.3656 ± 0.1056 and 0.7296 ± 0.1933, respectively) were observed. Altered BACE1, miR-15a-5p, and miR-19b-3p expressions suggest novel indicators for early LOAD diagnosis. We illustrated target genes by which these microRNAs may regulate BACE1 expression.

摘要

β-分泌酶1(BACE1)促进阿尔茨海默病患者大脑中β-淀粉样蛋白的聚集。微小RNA在基因表达调控中发挥作用。此外,BACE1是微小RNA的一个作用靶点。在阿尔茨海默病的病因学中,外周和中枢免疫系统之间存在相互作用。本研究调查晚发型阿尔茨海默病(LOAD)患者外周血单个核细胞(PBMCs)中BACE1以及miR-15a-5p和miR-19b-3p基因表达的变化。采用实时定量PCR方法检测PBMCs中BACE1 mRNA、miR-15a-5p和miR-19b-3p的水平。使用Cytoscape软件鉴定这些微小RNA的潜在靶基因。观察到BACE1水平显著升高(平均值±标准差:2.076±0.5308),miR-15a-5p和miR-19b-3p表达均降低(分别为0.3656±0.1056和0.7296±0.1933)。BACE1、miR-15a-5p和miR-19b-3p表达的改变提示了早期LOAD诊断的新指标。我们阐明了这些微小RNA可能调控BACE1表达的靶基因。

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