Study Rationale:
This project aims to find biomarkers for the diagnosis and prognosis of Parkinson's disease (PD). Levels of alpha-synuclein, a protein associated with the pathogenic mechanism of PD, are determined using a tailored-designed assay (analytic test), which is based on the biochemical property of how alpha-synuclein binds lipids (fat). Total and specific pathogenic forms of alpha-synuclein will be determined in blood samples obtained from the BioFIND clinical study, including samples from healthy participants and those with moderate and severe PD. Additional blood parameters, including markers of oxidative stress, will be determined in blood cells.
Hypothesis:
The expression of alpha-synuclein in blood cells is regulated independently of its expression in the brain. Our hypothesis is that alpha-synuclein in blood cells may serve as an indicator of peripheral pathogenic changes that are associated with PD onset in the brain. Therefore, blood cells expressing alpha-synuclein may potentially represent an early stage of the disease in the peripheral system prior to its occurrence in the brain.
Study Design:
The amount of total alpha-synuclein, as well as pathogenic form(s) of alpha-synuclein, that resist digestion by proteinase-K, will be determined in samples of whole blood pellets using our novel phospholipid assay. Alpha-synuclein levels will be compared between a group of healthy participants and those with PD, including moderate and severe cases of PD. The detected alpha-synuclein levels will be normalized to markers of oxidative stress and additional blood parameters. Using statistical analyses, we will search for correlations between alpha-synuclein levels and clinical symptoms, including severity of disease and occurrence of motor and non-motor symptoms.
Impact on Diagnosis/Treatment of Parkinson's Disease:
The development of a measurable and accessible biomarker, which reflects disease severity and progression, is essential for accurate diagnosis and for a measurable response to therapy. Such a biomarker will assist those affected with PD by providing accurate diagnosis and will promote drug development by providing a reliable indication of efficacy of treatment.
Next Steps for Development:
Following validation of the method and the biomarker for its accuracy to diagnose PD, we will perform a longitudinal study, to determine the feasibility of measuring blood cells expressing alpha-synuclein as a marker for pre-symptomatic, early detection of PD.