Zafari Sachli, Backes Christina, Meese Eckart, Keller Andreas
Clinical Bioinformatics, Saarland University, Saarbrx00FC;cken, Germany.
Gerontology. 2015;61(6):497-503. doi: 10.1159/000375236. Epub 2015 Feb 25.
The early diagnosis of diseases frequently represents an important unmet clinical need supporting in-time treatment of pathologies. This also applies to neurodegenerative diseases such as Alzheimer's disease (AD), the most common form of dementia, estimated to affect millions of individuals worldwide. The respective diagnostic and prognostic markers, especially for the preclinical stages of AD, are expected to improve patients' outcome significantly. In the last decades, many approaches to detecting AD have been developed, including markers to discover changes in amyloid-β levels [from cerebrospinal fluid (CSF) or using positron emission tomography] or other brain imaging technologies such as structural magnetic resonance imaging (MRI), functional-connectivity MRI or task-related functional MRI. A major challenge is the detection of AD using minimally or even noninvasive biomarkers from body fluids such as plasma or serum. Circulating biomarker candidates based on mRNAs or proteins measured from blood cells, plasma or serum have been proposed for various pathologies including AD. As for other diseases, there is a tendency to use marker signatures obtained by high-throughput approaches, which allow the generation of profiles of hundreds to thousands of biomarkers simultaneously [microarrays, mass spectrometry or next-generation sequencing (NGS)]. Beyond mRNAs and proteins, recent approaches have measured small noncoding RNA (so-called microRNA) profiles in AD patients' blood samples using NGS or array-based technologies. Generally, the development of marker panels is in its early stages and requires further, substantial clinical validation. In this review, we provide an overview of different circulating AD biomarkers, starting with a brief summary of CSF markers and focusing on novel biomarker signatures such as small noncoding RNA profiles.
疾病的早期诊断常常是一项重要的未满足的临床需求，它有助于及时治疗各种病症。这同样适用于神经退行性疾病，如阿尔茨海默病（AD），这是最常见的痴呆形式，据估计全球有数百万人受其影响。相应的诊断和预后标志物，特别是针对AD临床前期的标志物，有望显著改善患者的治疗效果。在过去几十年里，已经开发出许多检测AD的方法，包括用于发现淀粉样β水平变化的标志物（来自脑脊液或使用正电子发射断层扫描），以及其他脑成像技术，如结构磁共振成像（MRI）、功能连接MRI或任务相关功能MRI。一个主要挑战是使用来自血浆或血清等体液的微创甚至无创生物标志物来检测AD。基于从血细胞、血浆或血清中测量的mRNA或蛋白质的循环生物标志物候选物已被提出用于包括AD在内的各种病症。与其他疾病一样，存在使用高通量方法获得的标志物特征的趋势，这种方法能够同时生成数百至数千种生物标志物的图谱（微阵列、质谱或下一代测序）。除了mRNA和蛋白质，最近的方法还使用下一代测序或基于阵列的技术测量了AD患者血液样本中的小非编码RNA（所谓的微小RNA）图谱。一般来说，标志物组合的开发尚处于早期阶段，需要进一步进行大量的临床验证。在这篇综述中，我们概述了不同的循环AD生物标志物，首先简要总结脑脊液标志物，然后重点关注新型生物标志物特征，如小非编码RNA图谱。
