Nigrosome-1 neuromelanin and iron coupling in idiopathic and GBA-associated Parkinson disease
Parkinson’s disease (PD) involves early neuromelanin (NM) loss, iron dysregulation and often shows asymmetric motor onset. We quantified NM- and iron-sensitive MRI measures in the substantia nigra pars compacta (SNc) and nigrosome-1 (N1) in idiopathic PD (iPD, n = 30), GBA -associated PD (GBA-PD, n = 26) and in healthy controls (HC, n = 30), by performing magnitude-based metrics, asymmetry indices and cross-modal coupling analyses. Both PD groups showed reduced NM-sensitive and increased iron-sensitive signal relative to HC, with the strongest alterations in N1. NM-sensitive N1 markers provided the best patient-control discrimination, particularly between GBA-PD and HC (AUCLOOCV = 0.91). N1 NM asymmetry and most robustly N1 NM contrast ratio (CR), moderately distinguished HC from patient subgroups (AUCLOOCV range = 0.71-0.72). Asymmetry index (AI) metrics did not differentiate iPD from GBA-PD. The NM-iron coupling pattern observed in HC was inverted in PD. Exploratory analyses suggested a GBA1 severity-related variation in N1 NM-iron coupling. These findings identify N1 as the main subregion where multimodal MRI captures the PD-related nigral degeneration.
Authors
- Alícia Garrido (ORCID: https://orcid.org/0000-0003-0652-6348)
- Víctor Puente
- Ignacio Álvarez (ORCID: https://orcid.org/0000-0002-8537-3935)
- Mikel Ariz (ORCID: https://orcid.org/0000-0002-7328-1582)
- Mario Ezquerra (ORCID: https://orcid.org/0000-0003-3246-6641)
- Juan Marín‐Lahoz (ORCID: https://orcid.org/0000-0003-0008-2360)
- Gabriel Castellanos (ORCID: https://orcid.org/0000-0001-8121-1552)
- Katrin Beyer (ORCID: https://orcid.org/0000-0001-8905-1514)
- Pau Pástor (ORCID: https://orcid.org/0000-0002-7493-8777)
- Francesc Valldeoriola (ORCID: https://orcid.org/0000-0002-8680-4274)
- Nuria Suelves Caballol (ORCID: https://orcid.org/0000-0003-3363-3077)
- Carlos Ortíz-de-Solórzano (ORCID: https://orcid.org/0000-0001-8720-0205)
- Berta Pascual‐Sedano (ORCID: https://orcid.org/0000-0002-9298-8241)
- Maríateresa Buongiorno (ORCID: https://orcid.org/0000-0002-1745-5744)
- Jorge Hernández‐Vara (ORCID: https://orcid.org/0000-0002-9129-5224)
- Àngels Bayés (ORCID: https://orcid.org/0000-0001-9542-804X)
- María A. Pastor (ORCID: https://orcid.org/0000-0003-2404-9346)
- Dolores Vilas (ORCID: https://orcid.org/0000-0003-3084-053X)
- Yaroslau Compta (ORCID: https://orcid.org/0000-0001-6443-0104)
- Juan Pablo Tartari (ORCID: https://orcid.org/0000-0002-7548-2687)
- Martı́n Martı́nez (ORCID: https://orcid.org/0000-0002-3053-7920)
- Tomás Muñoz Santoro (ORCID: https://orcid.org/0009-0009-8065-3194)
- Miquel Aguilar
- Eduard S. Tolosa (ORCID: https://orcid.org/0000-0002-3781-0854)
- Alex Menéndez
- Asuncion Avila
- Maria Jose Marti
- Claustre Pont
Institutions
- Universitat Autònoma de Barcelona (ES)
- Universidad Pública de Navarra (UPNA) (ES)
- Hospital de Sant Pau (ES)
- Universidad Nacional de Colombia (CO)
- Hospital Quirón Teknon (ES)
- Vall d'Hebron Institut de Recerca (ES)
- Hospital General de Granollers (ES)
- Navarre Institute of Health Research (ES)
- Hospital Clínic de Barcelona (ES)
- Fundació ACE (ES)
- Vall d'Hebron Hospital Universitari (ES)
- Mútua Terrassa (ES)
- Hospital Del Mar (ES)
- Hospital de Sant Joan Despí Moisès Broggi (ES)
- Clinica Universidad de Navarra (ES)
- Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol (ES)
- Hospital Universitari Germans Trias i Pujol (ES)
- Centro de Investigación Biomédica en Red de Cáncer (ES)
- Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES)
- Centro de Investigación Médica Aplicada (ES)
- Universitat de Barcelona (ES)
- Universidad de Navarra (ES)
Publication Details
- Journal
- npj Parkinson s Disease
- Published
- 2026-10-28
- DOI
- https://doi.org/10.1038/s41531-026-01599-y
- Primary Topic
- Parkinson's Disease Mechanisms and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00