Kim Dana, Paik Jin Hui, Shin Dong-Woon, Kim Hak-Su, Park Chang-Shin, Kang Ju-Hee
Department of Pharmacology, Inha University School of Medicine, Korea. ; Hypoxia-related Disease Research Center, Inha University School of Medicine, Korea.
Department of Emergency Medicine, Inha University Hospital, Incheon 400-712, Korea.
Exp Neurobiol. 2014 Dec;23(4):352-64. doi: 10.5607/en.2014.23.4.352. Epub 2014 Dec 12.
The clinical diagnostic criteria of Parkinson's disease (PD) have limitations in detecting the disease at early stage and in differentiating heterogeneous clinical progression. The lack of reliable biomarker(s) for early diagnosis and prediction of prognosis is a major hurdle to achieve optimal clinical care of patients and efficient design of clinical trials for disease-modifying therapeutics. Numerous efforts to discover PD biomarkers in CSF were conducted. In this review, we describe the molecular pathogenesis of PD and discuss its implication to develop PD biomarkers in CSF. Next, we summarize the clinical utility of CSF biomarkers including alpha-synuclein for early and differential diagnosis, and prediction of PD progression. Given the heterogeneity in the clinical features of PD and none of the CSF biomarkers for an early diagnosis have been developed, research efforts to develop biomarkers to predict heterogeneous disease progression is on-going. Notably, a rapid cognitive decline followed by the development of dementia is a risk factor of poor prognosis in PD. In connection to this, CSF levels of Alzheimer's disease (AD) biomarkers have received considerable attention. However, we still need long-term longitudinal observational studies employing large cohorts to evaluate the clinical utility of CSF biomarkers reflecting Lewy body pathology and AD pathology in the brain. We believe that current research efforts including the Parkinson's Progression Markers Initiative will resolve the current needs of early diagnosis and/or prediction of disease progression using CSF biomarkers, and which will further accelerate the development of disease-modifying therapeutics and optimize the clinical management of PD patients.
帕金森病（PD）的临床诊断标准在疾病早期检测及区分异质性临床进展方面存在局限性。缺乏用于早期诊断和预后预测的可靠生物标志物是实现患者最佳临床护理以及设计针对疾病修饰疗法的有效临床试验的主要障碍。人们为在脑脊液中发现PD生物标志物付出了诸多努力。在本综述中，我们描述了PD的分子发病机制，并讨论其对开发脑脊液中PD生物标志物的意义。接下来，我们总结了脑脊液生物标志物的临床应用，包括α-突触核蛋白在早期和鉴别诊断以及预测PD进展方面的应用。鉴于PD临床特征的异质性，且尚未开发出用于早期诊断的脑脊液生物标志物，目前正在进行开发预测异质性疾病进展的生物标志物的研究工作。值得注意的是，快速认知衰退随后发展为痴呆是PD预后不良的一个危险因素。与此相关的是，阿尔茨海默病（AD）生物标志物的脑脊液水平受到了相当多的关注。然而，我们仍需要采用大型队列的长期纵向观察性研究来评估反映大脑路易体病理和AD病理的脑脊液生物标志物的临床应用。我们相信，包括帕金森病进展标志物倡议在内的当前研究工作将解决目前使用脑脊液生物标志物进行早期诊断和/或预测疾病进展的需求，这将进一步加速疾病修饰疗法的开发并优化PD患者的临床管理。
