Department of Animal Biology, Faculty of Natural Science, University of Tabriz, Tabriz, Iran.
Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
J Mol Neurosci. 2019 Nov;69(3):351-359. doi: 10.1007/s12031-019-01364-2. Epub 2019 Jul 1.
Circulating long noncoding RNAs (lncRNAs) might serve as biomarkers for different pathological conditions. BACE1-AS lncRNA upregulates in the brain of people with Alzheimer's disease (AD) and might be detected in the bloodstream. To reveal if lncRNA BACE1-AS may serve as a blood-based biomarker for AD, we compared its levels in plasma and plasma-derived exosomes between AD (n = 45) and healthy people (n = 36). Exosomes were purified from plasma by Invitrogen™ Total Exosome Isolation Kit and characterized by scanning electron microscopy (SEM) and dynamic light scattering (DLS). Total RNA was extracted from whole plasma, and plasma-derived exosomes using TRIzol® LS or TRIzol® Reagents respectively were then reverse transcribed to the cDNA using PrimeScript II cDNA synthesis kit. The BACE1-AS levels were quantified by real-time PCR, and their biomarker potencies were evaluated using ROC curve analysis. Results obtained verified the presence of BACE1-AS in the plasma samples of both AD and healthy controls. We did not observe any significant differences between the levels of BACE1-AS in the plasma or plasma-derived exosomes of AD and control people. However, there were significant differences between AD subgroups and control in the whole plasma samples. The BACE1-AS level was low in pre-AD subgroup but it was high in full-AD people compared to the healthy controls. Moreover, ROC curve analysis revealed that lncRNA BACE1-AS may discriminate pre-AD and healthy control (75% sensitivity and 100% specificity), full-AD and healthy control (68% sensitivity and 100% specificity), and pre-AD and full-AD subgroups (78% sensitivity and 100% specificity), highlighting its potential as a biomarker for AD development. In conclusion, plasma BACE1-AS level may serve as a potent blood-based biomarker for Alzheimer's disease.
循环长非编码 RNA(lncRNA)可能作为不同病理状态的生物标志物。BACE1-AS lncRNA 在阿尔茨海默病(AD)患者的大脑中上调,可能在血液中检测到。为了揭示 lncRNA BACE1-AS 是否可作为 AD 的基于血液的生物标志物,我们比较了 AD(n=45)和健康人(n=36)血浆和血浆衍生外泌体中的 BACE1-AS 水平。通过 Invitrogen™ Total Exosome Isolation Kit 从血浆中纯化外泌体,并通过扫描电子显微镜(SEM)和动态光散射(DLS)进行表征。使用 TRIzol® LS 或 TRIzol® Reagents 分别从全血浆和血浆衍生外泌体中提取总 RNA,然后使用 PrimeScript II cDNA 合成试剂盒将其反转录为 cDNA。通过实时 PCR 定量 BACE1-AS 水平,并通过 ROC 曲线分析评估其生物标志物潜力。结果证实 AD 和健康对照者的血浆样品中存在 BACE1-AS。我们没有观察到 AD 和对照组之间血浆或血浆衍生外泌体中 BACE1-AS 水平的任何显著差异。然而,在整个血浆样本中,AD 亚组与对照组之间存在显著差异。与健康对照组相比,BACE1-AS 水平在早期 AD 亚组中较低,但在完全 AD 人群中较高。此外,ROC 曲线分析显示,lncRNA BACE1-AS 可能区分早期 AD 和健康对照(75%的敏感性和 100%的特异性)、完全 AD 和健康对照(68%的敏感性和 100%的特异性)以及早期 AD 和完全 AD 亚组(78%的敏感性和 100%的特异性),突出了其作为 AD 发展生物标志物的潜力。总之,血浆 BACE1-AS 水平可能作为阿尔茨海默病的有效基于血液的生物标志物。