Institut de Neurociències and Dpt. Bioquímica i Biología Molecular, Universitat Autònoma de Barcelona, 08193, Cerdanyola del Vallès, Spain.
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
Alzheimers Res Ther. 2019 May 15;11(1):46. doi: 10.1186/s13195-019-0501-4.
Several evidences suggest that failure of synaptic function occurs at preclinical stages of Alzheimer's disease (AD) preceding neuronal loss and the classical AD pathological hallmarks. Nowadays, there is an urgent need to identify reliable biomarkers that could be obtained with non-invasive methods to improve AD diagnosis at early stages. Here, we have examined plasma levels of a group of miRNAs related to synaptic proteins in a cohort composed of cognitive healthy controls (HC), mild cognitive impairment (MCI) and AD subjects.
Plasma and brain levels of miRNAs were analysed in two different cohorts including 38 HC, 26 MCI, 56 AD dementia patients and 27 frontotemporal dementia (FTD) patients. D'Agostino and Pearson and Shapiro-Wilk tests were used to evaluate data normality. miRNA levels between groups were compared using a two-sided nonparametric Mann-Whitney test and sensitivity and specificity was determined by receiver operating characteristic curve analysis.
Significant upregulation of miR-92a-3p, miR-181c-5p and miR-210-3p was found in the plasma of both MCI and AD subjects. MCI patients that progress to AD showed higher plasma levels of these miRNAs. By contrast, no changes in miR-92a-3p, miR-181c-5p or miR-210-3p levels were observed in plasma obtained from a cohort of FTD.
Our study shows that plasma miR-92a-3p, miR-181c-5p and miR-210-3p constitute a specific molecular signature potentially useful as a potential biomarker for AD.
有几项证据表明，在神经元丧失和经典 AD 病理标志物之前，突触功能的失败就已经发生在阿尔茨海默病（AD）的临床前阶段。如今，人们迫切需要识别可靠的生物标志物，这些标志物可以通过非侵入性方法获得，以提高早期 AD 的诊断水平。在这里，我们检查了由认知健康对照（HC）、轻度认知障碍（MCI）和 AD 患者组成的队列中与突触蛋白相关的一组 miRNA 的血浆水平。
在包括 38 名 HC、26 名 MCI、56 名 AD 痴呆患者和 27 名额颞叶痴呆（FTD）患者的两个不同队列中分析了 miRNA 的血浆和大脑水平。使用 D'Agostino 和 Pearson 和 Shapiro-Wilk 检验来评估数据的正态性。使用双侧非参数 Mann-Whitney 检验比较组间 miRNA 水平，并通过接收者操作特征曲线分析确定灵敏度和特异性。
在 MCI 和 AD 患者的血浆中发现 miR-92a-3p、miR-181c-5p 和 miR-210-3p 显著上调。进展为 AD 的 MCI 患者表现出更高水平的这些 miRNA。相比之下，在来自 FTD 队列的血浆中未观察到 miR-92a-3p、miR-181c-5p 或 miR-210-3p 水平的变化。
我们的研究表明，血浆 miR-92a-3p、miR-181c-5p 和 miR-210-3p 构成了一个特定的分子特征，可能作为 AD 的潜在生物标志物有用。
