Biological Markers in Parkinson's Disease

OBJECTIVE: Parkinson's disease (PD) is a progressive neurodegenerative disorder of unknown etiology in which several underlying pathophysiological mechanisms including proteasomal degradation, mitochondrial dysfunction, inflammation, oxidative stress, and excitotoxicity may contribute to cell death. No treatment is known to cure or delay progression of PD, thus there is a need to investigate measurable biologic markers for the purpose of diagnosis, monitoring disease progression and effect of treatment. This study will focus on alpha synuclein and its metabolic pathways as a potential biomarker, to assist in evaluation of pathogenesis and future diagnostic and therapeutic options. STUDY POPULATION: In this pilot study we plan to include 30 patients with Parkinson's disease (PD), 30 patients with Parkinson plus disorders, and 30 control patients without neurologic disease or autoimmune disorders. DESIGN: Samples of serum, plasma and cerebrospinal fluid (CSF) will be collected from all patients for analysis at the beginning of the study. The assay will be performed for various proteins including cytokines primarily related to the alpha synuclein (AS) pathway. A repeat CSF, plasma and serum analysis will be performed in patients with PD, and Parkinson plus disorders at the end of one and two years to follow changes of protein expression profiles with disease progression. ASSESSMENT OF RISKS AND BENEFITS: This study will carry the risk associated with venepuncture and lumbar puncture. OUTCOME ESTIMATE AND POTENTIAL MEANING FOR THE FIELD: The primary outcome measure is to correlate the changes of alpha synuclein phosphorylation in CSF, plasma and serum with changes in UPDRS motor score in patients with PD over the period of 2 years, compared to controls. The secondary aim of the study is to compare the protein expression profiles between different synucleinopathies including PD, Multiple System Atrophy (MSA) and Dementia with Lewy Bodies (DLB) with time. There are currently no validated surrogate disease markers in PD or other related neurodegenerative disorders. Our work would hopefully help understand pathophysiologic mechanisms in patients with PD, monitor disease progression using specific biologic markers, and in future development of targeted therapies.