Longitudinal neuromelanin changes in prodromal and early Parkinson's disease in humans and rat model.

Abstract

Neuromelanin-sensitive MRI has been proposed as a biomarker of Parkinson's disease pathology. However, the biological and physical origins of this contrast are debated. A recent rodent model of controlled neuromelanin accumulation in the substantia nigra has been developed and recapitulates several features of Parkinson's disease. In this work, we first combined neuromelanin-sensitive-MRI and histology to study neuromelanin accumulation and neurodegeneration in a humanized rat model of Parkinson's disease. Neuromelanin-sensitive-MRI signal changes were biphasic with an initial increase due to the accumulation of neuromelanin in dopaminergic neurons, followed signal decrease due to neurodegeneration. In healthy subjects and patients with isolated rapid eye movement sleep behaviour disorder, neuromelanin-sensitive-MRI signal increased initially and then decreased similarly as in rodents after reaching a similar maximum signal intensity in both groups. In early Parkinson's disease and converted isolated rapid eye movement sleep behaviour disorder patients, neuromelanin-sensitive-MRI signal drop was greater than in healthy individuals. Results in animals and humans show that neuromelanin-sensitive-MRI is a marker of the intracellular neuromelanin accumulation and then of neuronal degeneration and originates mainly from T₁ reduction effect of neuromelanin.