PDF(Pubmed)
Abstract：
Alzheimer\'s disease (AD) is the most common cause of dementia. New strategies for the early detection of MCI and sporadic AD are crucial for developing effective treatment options. Current techniques used for diagnosis of AD are invasive and/or expensive, so they are not suitable for population screening. Cerebrospinal fluid (CSF) biomarkers such as amyloid β1-42 (Aβ1-42), total tau (T-tau), and phosphorylated tau181 (P-tau181) levels are core biomarkers for early diagnosis of AD. Several studies have proposed the use of blood-circulating microRNAs (miRNAs) as potential novel early biomarkers for AD. We therefore applied a novel approach to identify blood-circulating miRNAs associated with CSF biomarkers and explored the potential of these miRNAs as biomarkers of AD. In total, 112 subjects consisting of 28 dementia due to AD cases, 63 MCI due to AD cases, and 21 cognitively healthy controls were included. We identified seven Aβ1-42-associated plasma miRNAs, six P-tau181-associated plasma miRNAs, and nine Aβ1-42-associated serum miRNAs. These miRNAs were involved in AD-relevant biological processes, such as PI3K/AKT signaling. Based on this signaling pathway, we constructed an miRNA-gene target network, wherein miR-145-5p has been identified as a hub. Furthermore, we showed that miR-145-5p performs best in the prediction of both AD and MCI. Moreover, miR-145-5p also improved the prediction performance of the mini-mental state examination (MMSE) score. The performance of this miRNA was validated using different datasets including an RT-qPCR dataset from plasma samples of 23 MCI cases and 30 age-matched controls. These findings indicate that blood-circulating miRNAs that are associated with CSF biomarkers levels and specifically plasma miR-145-5p alone or combined with the MMSE score can potentially be used as noninvasive biomarkers for AD or MCI screening in the general population, although studies in other AD cohorts are necessary for further validation.
摘要：
阿尔茨海默病(AD)是痴呆的最常见原因。早期发现MCI和散发性AD的新策略对于开发有效的治疗方案至关重要。目前用于诊断AD的技术是侵入性的和/或昂贵的。所以它们不适合人群筛查。脑脊液（CSF）生物标志物，如淀粉样蛋白β1-42（Aβ1-42），总tau（T-tau），磷酸化tau181(P-tau181)水平是AD早期诊断的核心生物标志物。一些研究已经提出使用血液循环微小RNA(miRNA)作为AD的潜在新型早期生物标志物。因此，我们应用了一种新的方法来鉴定与CSF生物标志物相关的血液循环miRNA，并探索了这些miRNA作为AD生物标志物的潜力。总的来说,112名受试者由28名因AD病例引起的痴呆组成，63例由于AD病例引起的MCI，纳入21名认知健康对照.我们鉴定了7个与Aβ1-42相关的血浆miRNAs，六个P-tau181相关血浆miRNA，和9个Aβ1-42相关的血清miRNAs。这些miRNA参与AD相关的生物过程,如PI3K/AKT信号。基于这个信号通路,我们构建了一个miRNA-基因靶网络，其中miR-145-5p已被鉴定为中心。此外，我们发现miR-145-5p在预测AD和MCI方面表现最好.此外，miR-145-5p还改善了简易精神状态检查(MMSE)评分的预测性能。使用不同的数据集(包括来自23个MCI病例和30个年龄匹配对照的血浆样品的RT-qPCR数据集)来验证该miRNA的性能。这些发现表明，与CSF生物标志物水平相关的血液循环miRNA，特别是血浆miR-145-5p单独或与MMSE评分组合，可潜在地用作普通人群中AD或MCI筛查的非侵入性生物标志物。尽管其他AD队列的研究对于进一步验证是必要的。
