We have reported recently higher levels of α-synuclein oligomers species in cerebral spinal fluid (CSF) from patients clinically diagnosed with Parkinson’s disease (PD) versus control subjects. Interestingly, levels of o-α-syn were even higher in patients with mild PD and patients with early PD compared to the control group. The ultimate objectives of our proposal are to validate the quantification α-synuclein species in CSF, as surrogate biomarkers for PD, and to evaluate any changes with the clinical features of PD.
In order for us to validate the potential use of α-synuclein species as surrogate biomarker for PD progression, we need to analyze large CSF samples collected at different time points from a cohort of early diagnosed people with PD. In this proposal we will investigate CSF samples from the DATATOP cohort to validate our biomarkers, to evaluate any changes of α-synuclein species with clinical changes and/or progression of PD. We are proposing to analyze CSF samples that were taken at baseline and endpoint. The levels of CSF AD biomarkers will also be measured which are validated markers of neurodegeneration. We will then analyze the correlation with the clinical data and the levels of CSF α-syn-, Aβ- and tau-species with respect to the rate of disease progression, motor (UPDRS off) scores, cognitive (MMSE), etc.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Rapidly advancing basic research is creating an expanding pipeline of candidate disease-modifying therapeutics for PD that are entering clinical trials. However, progression and diagnostic biomarkers are needed in drug development for PD. The ultimate goal of our proposal is to validate the potential use of α-synuclein species in CSF as progression markers for PD.
If we validate our findings that α-synuclein oligomeric species are good surrogate biomarkers for PD progression, then our study will provide diagnostic tools that will help to identify individuals at risk of developing PD who have a less complete loss of dopamine neurons. At an early stage of the disease, the patients would be most responsive to and benefit most from a neuroprotective therapy. Markers that can serve as surrogates of therapeutic effect are also needed for clinical trials.
We analyzed 147 cerebrospinal spinal fluid (CSF) samples from DATATOP cohort that were taken at baseline and during follow-up visits. We measured the levels of alpha-synuclein protein and its modified forms as potential biomarkers for Parkinson’s disease. We also measured the Alzheimer’s disease biomarkers in this cohort. We then calculated the correlation between every single or combined biomarker and the clinical parameters measured in each patient. Our preliminarily statistical analyses showed significant correlations between alpha-synuclein species and some of the clinical parameters associated with Parkinson’s disease. Our findings support the potential use of alpha-synuclein as a segregate marker to diagnose Parkinson’s disease.