Study Rationale: The pathological changes observed in the brain tissue of people with Parkinson’s disease (PD) compared to healthy individuals motivated researchers to explore alpha-synuclein as a biomarker for PD. However, multiple studies have demonstrated that measuring the forms of alpha-synuclein present in the plasma and cerebrospinal fluid (CSF) does not yield high diagnostic accuracy. A more accurate representation of the alpha-synuclein species present in the brain could come from an examination of extracellular vesicles (EVs), small fluid-filled sacs secreted by neurons. This project aims to evaluate alpha-synuclein species contained in EVs derived from CSF and plasma as biomarkers for PD.
Hypothesis: We hypothesize that the forms of alpha-synuclein isolated from EVs will have higher diagnostic accuracy for PD than alpha-synuclein freely circulating in biofluids.
Study Design: We plan to develop a framework for analyzing alpha-synuclein species found in EVs that are isolated from either CSF or plasma, and we will evaluate the potential of this approach as a noninvasive PD diagnostic assay. This framework will include EV isolation and the specific detection of alpha-synuclein species carried by these EVs with high sensitivity. We will validate and optimize the method using samples collected from people with PD as well as healthy individuals.
Impact on Diagnosis/Treatment of Parkinson’s disease: If successful, our method will lead to much more specific and sensitive assays for detecting alpha-synuclein pathology—a result that would have a significant impact on the diagnosis of PD.
Next Steps for Development: If our study is successful, we will apply our method to another set of samples that has been collected over time by MJFF to evaluate the potential of this assay for monitoring disease progression and supporting clinical trials.