Department of Clinical Laboratory, Shandong Provincial Hospital affiliated to Shandong University, Jinan, P. R. China.
Department of Neurology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, P. R. China.
J Alzheimers Dis. 2017;60(4):1365-1377. doi: 10.3233/JAD-170343.
Alzheimer's disease (AD) is the most common type of age-related neurodegenerative disorder; nevertheless, nowadays there are no reliable biomarkers or non-invasive techniques available for its early detection. Recent studies have indicated that the circulating level profiles of microRNAs (miRNAs) have the potential to be used as valuable biomarkers for diagnosis, staging, and progress monitoring of various diseases. Here we report a novel 9-miRNA signature (hsa-miR-26a-5p, hsa-miR-181c-3p, hsa-miR-126-5p, hsa-miR-22-3p, hsa-miR-148b-5p, hsa-miR-106b-3p, hsa-miR-6119-5p, hsa-miR-1246, and hsa-miR-660-5p) that can be utilized as biomarker for detecting AD. We respectively profiled the serum miRNAs from 19 AD patients and 9 healthy control (HC) participants using the Next-Generation Sequencing (NGS). The NGS results were validated by quantitative real-time polymerase chain reaction (qRT-PCR) on a larger cohort of 121 AD and 86 HC cases. All the patients were divided into three groups (mild, moderate, and severe AD) based on the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR). Our research indicates that abnormal expression of distinct serum miRNAs occurs at different stages of AD. The difference of the area under the receiver operator characteristics curve (AUC) between the AD and the HC is between 70% and 85%. Among the 9 miRNAs, hsa-miR-22-3p has the best sensitivity (81.8%) and specificity (70.9%). The miRNA-panel is more valuable for AD diagnosis. The data suggest that the differentially expressed serum miRNAs could be used as biomarkers to improve the diagnosis of AD, particularly at the early stage, and to classify its clinical stages.
阿尔茨海默病（AD）是最常见的与年龄相关的神经退行性疾病；然而，目前尚无可靠的生物标志物或非侵入性技术可用于早期检测。最近的研究表明，microRNAs (miRNAs) 的循环水平谱有可能成为各种疾病诊断、分期和进展监测的有价值的生物标志物。在这里，我们报告了一个新的 9 个 miRNA 特征（hsa-miR-26a-5p、hsa-miR-181c-3p、hsa-miR-126-5p、hsa-miR-22-3p、hsa-miR-148b-5p、hsa-miR-106b-3p、hsa-miR-6119-5p、hsa-miR-1246 和 hsa-miR-660-5p），可作为检测 AD 的生物标志物。我们分别使用下一代测序（NGS）对 19 名 AD 患者和 9 名健康对照（HC）参与者的血清 miRNAs 进行了分析。NGS 结果在更大的 121 名 AD 和 86 名 HC 病例队列中通过定量实时聚合酶链反应（qRT-PCR）进行了验证。所有患者根据简易精神状态检查（MMSE）和临床痴呆评定量表（CDR）分为三组（轻度、中度和重度 AD）。我们的研究表明，在 AD 的不同阶段，不同的血清 miRNAs 存在异常表达。AD 和 HC 之间的受试者工作特征曲线（ROC）下面积（AUC）差异在 70%至 85%之间。在 9 个 miRNA 中，hsa-miR-22-3p 的灵敏度（81.8%）和特异性（70.9%）最高。miRNA 谱对 AD 诊断更有价值。数据表明，差异表达的血清 miRNAs 可用作生物标志物，以提高 AD 的诊断水平，尤其是在早期阶段，并对其临床分期进行分类。
