Objective/Rationale:
One of the major challenges in biomarker discovery/validation for Parkinson's disease (PD) is to define their utility in PD progression. This task is best tackled with the samples collected longitudinally (e.g. DATATOP cohort) and ideally in at least a sub-cohort without being treated with any medicines. Consequently, we have planned to test a few novel/promising biomarkers discovered in the cerebrospinal fluid (CSF) collected in cross-sectional cohorts of PD patients in this precious DATATOP samples.
Project Description:
Most promising biomarkers discovered for PD thus far, e.g. DJ-1, α-synuclein and a few inflammatory cytokines, are based on CSF samples collected in cross-sectional cohorts (i.e. a snap shot of a disease that typically lasts for a few decades). In this study, we are planning to confirm/validate the best CSF candidate markers in an independent longitudinally collected DATATOP sample, where there is a significant subset of subjects who only received placebo medication. The technologies to be employed are immunoassays that have been used extensively in our lab already. The CSF values of these markers will be correlated with clinical performance of each subject (collected already by DATATOP investigators), with or without medications.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
To assess the performance of markers, especially those related to PD progression more effectively, it is important to use a cohort(s) with samples collected longitudinally and, ideally, without being treated with any dopamine medication (the main drugs to combat PD currently). PD progression markers, if identified, will impact PD research and clinical trials tremendously.
Anticipated Outcome:
We anticipate that a subset of markers tested will be correlated with PD progression in the longitudinally collected DATATOP samples
Final Outcome
DATATOP stands for Deprenyl and Tocopherol Antioxidative Therapy for Parkinson's Disease. It is a double-blinded, placebo controlled investigation, initiated over 20 years ago, where both collection of cerebrospinal fluid (CSF) and extensive clinical assessment of Parkinson’s patients were performed at baseline and then again when patients reached the endpoint, i.e. needing levodopa therapy to overcome motor disability. In this proposal, we took advantage of the cohort to validate a few best biomarkers of Parkinson’s disease, including alpha-synuclein and tau species that appear to be important in recent studies, in CSF samples collected longitudinally. At this point, we have analyzed seven markers in over 5,000 samples. Our results are still being analyzed, but tau species clearly show strong correlation with Parkinson’s disease progression. On the other hand, we did not observe any appreciable effects of deprenyl or tocopherol on the markers analyzed thus far.