Study Rationale: Parkinson's disease (PD) and dementia with Lewy bodies involve accumulation of alpha-synuclein in neurons. A recently developed test for alpha-synuclein aggregates in cerebrospinal fluid (CSF) allows disease identification; however, a quantitative blood test for measuring alpha-synuclein would provide a more accessible tool for disease diagnosis and could facilitate the evaluation of disease progression. The blood test we propose is based on nanosized vesicles released by neurons into the bloodstream, called neuron-derived extracellular vesicles. In previous work with over 100 patients, this test allowed us to detect significantly elevated levels of alpha-synuclein in comparison to healthy individuals.
Hypothesis: We hypothesize that measurement of alpha-synuclein in neuron-derived extracellular vesicles could replace the more invasive CSF aggregation assay and could provide a means to monitor longitudinal changes in disease progression.
Study Design: We previously developed the method for measuring the suggested biomarkers. This study therefore focuses on testing the clinical performance of this method in a well-curated cohort from the Parkinson's Progression Markers Initiative (PPMI). First, we will test a discovery cohort of 325 blood samples and compare our results with the CSF aggregation assay and monitoring of disease progression. Based on the results of this cohort, we will design a validation cohort of about 1200 samples to verify the biomarker performance. Our study will be performed in a good laboratory practice (GLP) environment, making the results ready for clinical use.
Impact on Diagnosis/Treatment of Parkinson’s Disease: Our method will provide a simpler and less invasive means of selecting individuals for clinical trials, particularly in the early stages of disease, when symptoms are not clear. The approach can also allow monitoring of disease progression and thus serve as a readout in clinical trials.
Next Steps for Development: This study is performed under good laboratory practice (GLP) and includes both discovery and validation cohorts; thus, positive results can be quickly translated to clinical trial practice. Potential follow-ups include a second large validation cohort, lab-to-lab validation and the establishment of a diagnosis cut-off.