Study Rationale: Parkinson’s disease is caused by the accumulation of misfolded alpha-synuclein, a protein that spreads in the brain and nervous system. Current cerebrospinal fluid (CSF) tests require an invasive spinal tap, limiting widespread use. A blood-based seed amplification assay (SAA) would enable easier, less invasive detection, but existing methods struggle with inhibitors in blood. This project integrates Nano-QuIC, which enhances SAA sensitivity using nanoparticles, with same-day RT-QuIC (sdRT-QuIC), which accelerates testing, into a single rapid, highly sensitive blood-based SAA for Parkinson’s disease.
Hypothesis: We hypothesize that integrating Nano-QuIC, which overcomes blood-based inhibitors using nanoparticles, with same-day RT-QuIC will enable a rapid, accurate, and highly sensitive blood-based seed amplification assay for detecting misfolded alpha-synuclein in Parkinson’s disease. This approach builds on advancements pioneered by NIH and our research teams.
Study Design: We will develop and optimize a blood-based test using Nano-QuIC to capture and amplify misfolded alpha-synuclein while maintaining the rapid turnaround of same-day RT-QuIC. First, we will standardize how blood samples are processed to ensure accurate and reproducible results. Next, we will fine-tune the testing method by combining these two approaches for optimal performance. Finally, we will validate the test using blinded blood samples from Parkinson’s patients and healthy controls from the Mayo Clinic MONITOR cohort, a well-characterized patient study, to assess accuracy and reliability.
Impact on Diagnosis/Treatment of Parkinson’s disease: A blood-based SAA test for Parkinson’s disease would revolutionize diagnosis by providing a fast, accessible, and minimally invasive alternative to spinal taps. It could be used for early detection, monitoring disease progression, and evaluating new treatments in clinical trials.
Next Steps for Development: If successful, our combined technology will undergo further validation in larger patient groups to ensure clinical accuracy. Ultimately, we aim to translate this technology into a widely available blood-based diagnostic tool to improve Parkinson’s disease detection and monitoring in both research and clinical settings.