Department of Neurology, Institut d'Investigacions Biomèdiques, Hospital de Sant Pau, Sant Antoni Maria, Claret 167, Barcelona 08025, Spain.
IRCCS Istituto Centro San Giovanni di Dio-Fatebenefratelli, Italy.
Nat Rev Neurol. 2015 Jan;11(1):41-55. doi: 10.1038/nrneurol.2014.232. Epub 2014 Dec 16.
Alzheimer disease (AD) and Parkinson disease (PD) are the most common neurodegenerative disorders. For both diseases, early intervention is thought to be essential to the success of disease-modifying treatments. Cerebrospinal fluid (CSF) can reflect some of the pathophysiological changes that occur in the brain, and the number of CSF biomarkers under investigation in neurodegenerative conditions has grown rapidly in the past 20 years. In AD, CSF biomarkers are increasingly being used in clinical practice, and have been incorporated into the majority of clinical trials to demonstrate target engagement, to enrich or stratify patient groups, and to find evidence of disease modification. In PD, CSF biomarkers have not yet reached the clinic, but are being studied in patients with parkinsonism, and are being used in clinical trials either to monitor progression or to demonstrate target engagement and downstream effects of drugs. CSF biomarkers might also serve as surrogate markers of clinical benefit after a specific therapeutic intervention, although additional data are required. It is anticipated that CSF biomarkers will have an important role in trials aimed at disease modification in the near future. In this Review, we provide an overview of CSF biomarkers in AD and PD, and discuss their role in clinical trials.
阿尔茨海默病（AD）和帕金森病（PD）是最常见的神经退行性疾病。对于这两种疾病，人们认为早期干预对于成功治疗疾病至关重要。脑脊液（CSF）可以反映大脑中发生的一些病理生理变化，在过去 20 年中，用于神经退行性疾病的 CSF 生物标志物的研究数量迅速增加。在 AD 中，CSF 生物标志物越来越多地用于临床实践，并已纳入大多数临床试验，以证明目标的结合，富集或分层患者群体，并寻找疾病修饰的证据。在 PD 中，CSF 生物标志物尚未进入临床，但正在帕金森病患者中进行研究，并在临床试验中用于监测进展或证明药物的目标结合和下游效应。CSF 生物标志物也可能作为特定治疗干预后临床获益的替代标志物，但需要更多的数据。预计 CSF 生物标志物将在未来针对疾病修饰的试验中发挥重要作用。在这篇综述中，我们概述了 AD 和 PD 中的 CSF 生物标志物，并讨论了它们在临床试验中的作用。
