Optimization of the Seed Amplification Assay (RT-QuIC) for early screening of synucleinopathies patients

Parkinson’s Disease (PD) is a neurodegenerative disorder characterized by motor symptoms, such as bradykinesia, rigidity and resting tremor. To this day, no effective treatment is capable to halt disease progression, with diagnosis relying on clinical manifestation of motor symptoms, which takes years to manifest. Early detection of the disease, then, is crucial for effective potential disease modifying intervention. In this regard, Real Time Quake-Induced Conversion (RT-QuIC) has shown high sensitivity in identifying PD patients, even at early stages of the pathology. Nevertheless, this technology only offers qualitative results, lacks standardized protocols and requires biofluids that are not easily accessible. Thus, we aimed at assessing unbiased quantitative parameters that could reflect disease progression and underline differences among synucleinopathies. In this study, we apply a statistical and mathematical approach to analyse the quantifiable parameters of the test and provide a standardized protocol through a rigorous characterization of the starting material. Our results offer a comprehensive view on the variables that affect the test’s outcome, thus helping to advance RT-QuIC into a more quantitative, standardized and less invasive test, potentially allowing for its usage as a routine exam in clinics to predict pathology manifestation.