The abnormal iron accumulation in Nigrosome-1 (N1) is a hallmark of Parkinson Disease (PD). It corresponds to the swallow tail sign loss and can be estimated using Quantitative Susceptibility Mapping. We investigated possible differences in N1 iron accumulation among gene-related PD patients, sporadic PD patients, PD-related gene mutation carriers and healthy controls (HCs).

Sixty-five subjects (8 LRRK2-PD, 13 GBA-PD, 21 sporadic PD, 7 LRRL2 carriers, 2 GBA carriers, 14 HCs) underwent a brain 7T-MRI including two 3D multi-echo GRE sequences, one for the qualitative assessment of the swallow tail sign and the other for measuring N1 magnetic susceptibility.

The swallow tail sign was lost in 90% of gene-related (75% of LRRK2-PD and 100% of GBA-PD patients) and 95% of sporadic PD patients, in 22% of carriers and in 14% of HCs.

N1 susceptibility was significantly higher in sporadic and gene-related PD patients than in carriers and HCs (p<0.005). Among gene-related PD patients, the high N1 susceptibility values were driven by GBA-PD (GBA-PD vs HCs, p<0.0001; LRRK2-PD vs HCs, p>0.5). Among all PD patients, GBA-PD showed the highest N1 susceptibility followed by sporadic PD (GBA-PD vs sporadic PD, p<0.01) and LRRK2-PD (GBA-PD vs LRRK2-PD, p<0.05; sporadic PD vs LRRK2-PD, p=0.3). N1 susceptibility in carriers did not differ from that of HCs.

The results showed that the abnormal N1 iron deposition is a finding shared by sporadic and gene-related PD patients, but the degree of iron accumulation varies across patient groups. This pattern might suggest differences in pathological mechanisms of neurodegeneration.