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.