Exp Neurobiol 2014; 23(4): 352-364
Published online December 31, 2014
© The Korean Society for Brain and Neural Sciences
Dana Kim1,2, Jin Hui Paik3, Dong-Woon Shin4, Hak-Su Kim1,2, Chang-Shin Park1,2 and Ju-Hee Kang1,2,5*
1Department of Pharmacology, 2Hypoxia-related Disease Research Center, Inha University School of Medicine,
3Department of Emergency Medicine, Inha University Hospital, Incheon 400-712,
4Department of Emergency Medicine, Inje University Ilsan Paik Hospital, Ilsan 411-706, Korea,
5Department of Pathology and Laboratory Medicine, Perelman School of Medicine,
University of Pennsylvania, Philadelphia, PA, 19104, USA
Correspondence to: *To whom correspondence should be addressed.
TEL: 82-32-890-0963, FAX: 82-32-887-7488
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.
Keywords: Parkinson’s disease, Biomarker, Cerebrospinal fluid, alpha-synuclein, Progression markers