Study Rationale: Individuals with Parkinson’s disease (PD) display variable impairment of the brain and peripheral nervous system, suggesting that PD includes a range of subtypes. Yet the underlying causes for this variation remain poorly understood. We are using advanced imaging techniques to categorize people newly diagnosed with PD according to their imaging profile, and investigate whether genetic risk factors or the gut microbiome can explain these different PD subtypes. Here, we will recruit three characteristic groups of subjects at increased PD risk to study how these PD subtypes appear before diagnosis and how they progress over time.
Hypothesis: We aim to demonstrate the existence of different PD subtypes and to show that these subtypes can be identified during the pre-diagnostic phase of the disease by means of their different “fingerprints” on a battery of scans.
Study Design: We will follow, over time, three groups of subjects with (1) pure autonomic failure, (2) GBA-mutations and (3) other risk factors for developing PD using multi-modal imaging, blood and stool sample analyses and biopsies. These groups represent different, but well characterized types of pre-diagnostic PD. We will compare these data with data from our expanding cohort of newly diagnosed PD patients and healthy volunteers. Samples and biopsies will be bio-banked to be used for future analyses of genetic and gut microbiome risk factors and different types of alpha-synuclein.
Impact on Diagnosis/Treatment of Parkinson’s disease: This study will improve our fundamental understanding of different PD subtypes, and how to recognize them before and after appearance of motor symptoms. These subtypes may have different genetic and molecular causes, and may therefore need different strategies for treatment and prevention in the future.
Next Steps for Development: The next step is to intensify research into the underlying causes of different PD subtypes and to further refine our abilities to diagnose them at the earliest possible stage. This is crucial for future clinical trials.