整合临床与转录组分析揭示连接听力损失与阿尔茨海默病认知衰退的miRNA介导机制
Integrated clinical and transcriptomic analysis reveals miRNA-mediated mechanisms linking hearing loss to cognitive decline in Alzheimer's disease.
文献信息
| PMID | 42968239 |
|---|---|
| 原文 | 在 PubMed 查看原文 ↗ |
| 发表日期 | 2026 |
| 作者 | Xin Wang |
| 作者单位 | Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China. |
| 期刊 | Journal of Alzheimer's disease : JAD |
| SCI 分区 | Q2 |
| IF | 4.1 |
| 研究类型 | 临床研究 · 临床 |
| 所属专科 | 耳科 |
中文摘要
背景： 听力损失（HL）是阿尔茨海默病（AD）的一个强有力的可改变危险因素，但其潜在分子机制仍不明确。鉴于microRNA（miRNA）在神经退行性变和听觉功能中的作用，它们是潜在的关键介质。目的：探讨伴与不伴HL的AD患者外周血miRNA谱是否存在差异，以及hsa-miR-6875-5p是否可作为候选分子连接。方法：在一项纳入41例AD患者（AD-HL n=24，AD-non-HL n=17）的病例对照研究中，我们进行了神经心理学评估、血浆miRNA测序、靶基因预测，并使用公共转录组数据集进行外部验证。结果：AD-HL患者在蒙特利尔认知评估和听觉词语学习测验延迟回忆评分上显著更差（p<0.05）。我们鉴定出9个差异表达的miRNA，其中hsa-miR-6875-5p上调最显著（3.29倍，p=0.041）。其预测靶基因富集于突触可塑性相关通路。在AD脑数据集中的外部验证支持hsa-miR-6875-5p一致上调以及SYN1/PSD95下调。在小鼠耳蜗数据集中的验证显示同源miRNA和靶基因的表达趋势一致。缺乏健康对照组使得无法确定该miRNA特征是否为AD-HL所特有，抑或为HL或AD的一般特征。结论：这项初步研究确定hsa-miR-6875-5p为连接AD中HL与认知衰退的潜在循环生物标志物。这些发现具有假说生成性质，需要在更大队列（包括健康对照）和功能实验中加以证实。
英文摘要
BackgroundHearing loss (HL) is a potent, modifiable risk factor for Alzheimer's disease (AD), but the underlying molecular mechanisms remain elusive. microRNAs (miRNAs) are potential key mediators given their roles in both neurodegeneration and auditory function.ObjectiveTo investigate whether peripheral blood miRNA profiles differ between AD patients with and without HL, and whether hsa-miR-6875-5p serves as a candidate molecular link.MethodsIn a case-control study of 41 AD patients (AD-HL n = 24, AD-non-HL n = 17), we performed neuropsychological assessments, plasma miRNA sequencing, target gene prediction, and external validation using public transcriptomic datasets.ResultsAD-HL patients showed significantly worse Montreal Cognitive Assessment and Auditory Verbal Learning Test delayed recall scores (p < 0.05). We identified 9 differentially expressed miRNAs, with hsa-miR-6875-5p being the most upregulated (3.29-fold, p = 0.041). Its predicted targets were enriched in synaptic plasticity-related pathways. External validation in AD brain datasets supported consistent upregulation of hsa-miR-6875-5p and downregulation of SYN1/PSD95. Validation in mouse cochlear datasets showed concordant expression trends for homologous miRNA and target genes. The absence of healthy control groups precludes determination of whether this miRNA signature is specific to AD-HL or a general feature of HL or AD.ConclusionsThis preliminary study identifies hsa-miR-6875-5p as a potential circulating biomarker linking HL to cognitive decline in AD. These findings are hypothesis-generating and require confirmation in larger cohorts, including healthy controls, and functional experiments.