Longitudinal neuromelanin changes in prodromal and early Parkinson’s disease in humans and rat model
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 T<sub>1</sub> reduction effect of neuromelanin.
Authors
- Marie Vidailhet (ORCID: https://orcid.org/0000-0002-2409-9143)
- Sana Rebbah
- Laura Mouton (ORCID: https://orcid.org/0000-0002-6698-3412)
- Arnaud Le Troter (ORCID: https://orcid.org/0000-0002-7897-9672)
- Mathieu Santin (ORCID: https://orcid.org/0000-0003-4251-0538)
- Rahul Gaurav (ORCID: https://orcid.org/0000-0001-9983-5873)
- Annabelle Parent (ORCID: https://orcid.org/0000-0002-6195-812X)
- Graziella Mangone (ORCID: https://orcid.org/0000-0002-2847-3067)
- J. Pérot (ORCID: https://orcid.org/0000-0002-6066-2909)
- Isabelle Arnulf (ORCID: https://orcid.org/0000-0002-2240-2516)
- Romain Valabrègue
- Lucas Soustelle (ORCID: https://orcid.org/0000-0002-4688-3262)
- François‐Xavier Lejeune (ORCID: https://orcid.org/0000-0002-6229-5364)
- Anthony Ruze
- Stéphane Lehéricy
- Jean-Christophe Corvol
- Capucine Cadin
Institutions
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Universitat Autònoma de Barcelona (ES)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Aix-Marseille Université (FR)
- Sorbonne Université (FR)
- Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
- Assistance Publique – Hôpitaux de Paris (FR)
- Vall d'Hebron Institut de Recerca (ES)
- Pitié-Salpêtrière Hospital (FR)
- Centre de Résonance Magnétique Biologique et Médicale (FR)
- Institut du Cerveau (FR)
- Research Network (United States) (US)
Publication Details
- Journal
- Brain Communications
- Published
- 2025-01-01
- DOI
- https://doi.org/10.1093/braincomms/fcaf204
- Citations
- 6
- Primary Topic
- Parkinson's Disease Mechanisms and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 8.34
Funders
- Michael J. Fox Foundation for Parkinson's Research
- Biogen
- EU Joint Programme – Neurodegenerative Disease Research
- Aligning Science Across Parkinson’s
- Agence Nationale de la Recherche
- Centre National de la Recherche Scientifique
- Fondation Saint Luc
- Instituto de Salud Carlos III