Detecting the pathogenic threshold of neuromelanin accumulation in Parkinson’s disease and prodromal Parkinson’s disease patients

Motivation: Neuromelanin is a pigment that accumulates specifically in neurons population that are vulnerable in Parkinson's disease. The role of neuromelanin in pathogenesis is still unclear. Goal(s): We tested the hypothesis that there is a pathogenic threshold of neuromelanin accumulation that triggers neurodegeneration in Parkinson's disease patients. Approach: We performed longitudinal neuromelanin-MRI imaging of the substantia nigra of Parkinson's disease, prodromal Parkinson's disease (iRBD) patients, and healthy volunteers. Results: We confirmed accelerated decrease of neuromelanin-MRI signal in patients with Parkinson's disease, which started from the maximum of healthy volunteer, in line with hypothetic pathogenic threshold. iRBD patients showed similar trajectory delayed by 5 years. Impact: Results support the hypothesis of a pathogenic threshold of neuromelanin. Its role in Parkinson's disease pathogenesis needs more investigations. Late reach of this threshold in prodromal patients results in delayed age of Parkinson's disease onset, suggesting different progression pattern.