Cerebrospinal fluid biomarkers for Parkinson's disease and L-DOPA-induced dyskinesia

Parkinson’s disease (PD) is a common disease, affecting 1% of the population older than 60 years of age[1]. Neuropathological characteristics of the disease include the presence of alpha-synuclein containing Lewy bodies in the brain stem and loss of nigrostriatal dopaminergic neurons, which result in motor deficits that are used as diagnostic criteria for PD[2].
So far there is no treatment available slowing the progression of PD. The otherwise effective dopamine replacement therapy not only loses its effectiveness during the natural course of the disease but also increases the risk of developing debilitating involuntary movements called L-DOPA-induced dyskinesia (LID)[3].
Developing drug treatments that slow the neurodegeneration in PD and prevents adverse effects of current drug treatments, including LID, requires not only a better understanding of the pathophysiology of PD and LID, but also the development of biomarkers for earlier and more precise diagnosis and prognosis.
The purpose of this study is the development and evaluation of proposed biomarkers in the cerebrospinal fluid (CSF) of rat models of PD and LID as well as in patients with early and late stage PD with or without LID. Potential biomarkers for PD such as alpha-synuclein and lysosomal enzymes[4] will be analyzed. In the rat model of LID extracellular regulated kinases (ERK1/2) and other signalling proteins will be studies through metabolomics and quantitative immunoassays. Promising biomarkers will subsequently be analysed in the CSF of patients, who are also clinically rated using the Unified Parkinson’s Disease rating scale (UPDRS)[5] and the Unified Dyskinesia Rating Scale (UDysRS).




1. de Lau LM, Breteler MM. Epidemiology of Parkinson's disease. Lancet neurology. 2006;5(6):525-35.
2. Rodriguez-Oroz MC, Jahanshahi M, Krack P, et al. Initial clinical manifestations of Parkinson's disease: features and pathophysiological mechanisms. Lancet neurology. 2009;8(12):1128-39.
3. Jenner P. Molecular mechanisms of L-DOPA-induced dyskinesia. Nature reviews Neuroscience. 2008;9(9):665-77.
4. Parnetti L, Castrioto A, Chiasserini D, et al. Cerebrospinal fluid biomarkers in Parkinson disease. Nature reviews Neurology. 2013;9(3):131-40.
5. Goetz CG, Tilley BC, Shaftman SR, et al. Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Movement disorders : official journal of the Movement Disorder Society. 2008;23(15):2129-70.