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.

The authors wish to thank all the participants of the study. These authors contributed equally: Martín Martínez, Mikel Ariz. These authors jointly supervised this work: Jorge Hernández-Vara, Carlos Ortiz de Solórzano, Maria A.

Neuroimaging Laboratory, School of Medicine, University of Navarra, Pamplona, Spain Cognitive and Affective Methods in Psychology, Department of Psychology, School of Education and Psychology, Pamplona, Spain CIBERONC and Biomedical Engineering Program, CIMA University of Navarra, Pamplona, Spain Mikel Ariz, Tomás Muñoz Santoro & Carlos Ortiz de Solórzano Department of Electrical, Electronic and Communication Engineering, Public University of Navarre (UPNA), Pamplona, Spain IdiSNA, Navarra Institute for Health Research, Pamplona, Spain Neurosciences, The Germans Trias i Pujol Research Institute (IGTP) Badalona, Barcelona, Spain Ignacio Alvarez, Katrin Beyer & Pau Pastor Department of Physiological Sciences, School of Medicine, Universidad Nacional de Colombia, Bogotá, Colombia Parkinson’s Disease and Movement Disorders Unit, Neurology, Hospital Clínic Universitari de Barcelona/UBNeuro/IDIBAPS, Barcelona, Spain Mario Ezquerra, Alicia Garrido, Maria Jose Marti, Francesc Valldeoriola, Eduard Tolosa & Yaroslau Compta Parkinson and Movement disorders Unit, Hospital Quirón-Teknon, Barcelona, Spain Unit of Neurodegenerative diseases, Department of Neurology, University Hospital Germans Trias i Pujol and Neurosciences, Badalona, Barcelona, Spain Alex Menendez, Dolores Vilas & Pau Pastor Movement Disorders Unit, Neurology, Hospital Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain Neurology Department, Hospital Universitari Vall D’Hebron. Neurodegenerative Diseases Research Group. Vall D’Hebron Research Institute (VHIR), Barcelona, Spain Department of Neurology, Clínica Universidad de Navarra, Pamplona, Spain School of Medicine, Autonomous University of Barcelona University of Barcelona (UAB)(UAB), Barcelona, Spain Department of Neurology, Complex Hospitalari Moisès Broggi, Barcelona, Spain Movement Disorders Unit, Neurology, Hospital Universitari Mútua de Terrassa, Barcelona, Spain Movement Disorders Unit, Neurology, Hospital del Mar, Barcelona, Spain Neurology Service, Hospital General de Granollers, Barcelona, Spain Correspondence to Jorge Hernández-Vara, Carlos Ortiz de Solórzano, Maria A.

No, I declare that the authors have no competing interests as defined by Nature Portfolio, or other interests that might be perceived to influence the results and/or discussion reported in this paper. Y.C. is an associate editor of Parkinsonism & Related Disorders. Y.C. was not involved in the journal’s review of, or decisions related to, this manuscript.