Study Rationale: Parkinson’s disease (PD) is associated with the accumulation of clumped alpha-synuclein (asyn) protein in the brain. Detecting asyn in blood plasma could provide a less invasive and more accessible method for diagnosing and monitoring PD. However, current methods face challenges in sensitivity, reproducibility, and quantification, particularly in blood, where asyn concentrations are very low. This project aims to overcome these challenges by developing a highly sensitive and automated assay to detect and measure misfolded asyn in plasma.
Hypothesis: We hypothesize that a quantitative alpha-synuclein seed amplification assay (aSyn-SAA) can accurately detect and measure disease progression in Parkinson’s disease using blood plasma samples.
Study Design: We will optimize an immunoprecipitation (IP) method to extract misfolded asyn seeds from blood plasma, improving sensitivity by removing interfering molecules. The extracted seeds will be analyzed using an advanced seed amplification assay (SAA), which amplifies the misfolded proteins for detection. To enhance accuracy and throughput, we will automate the assay using a high-capacity 1536-well platform. The optimized method will be validated using plasma samples from individuals with PD and related disorders, including longitudinal samples from the Harvard Biomarkers Study, to assess its ability to track disease progression over time.
Impact on Diagnosis/Treatment of Parkinson’s disease: This project has the potential to revolutionize how Parkinson’s disease is diagnosed and monitored by providing a minimally invasive blood test for detecting misfolded alpha-synuclein. A quantitative biomarker could also help evaluate the effectiveness of new therapies targeting alpha-synuclein.
Next Steps for Development: If successful, we will expand the assay to include broader populations of patients with Parkinson’s disease and other synucleinopathies, such as prodromal REM-sleep behavior disorder, dementia with Lewy bodies, and multiple system atrophy. Additionally, we will work toward making the assay more accessible for clinical use as a standardized diagnostic and monitoring tool.