Gradients of Nigrostriatal Iron Deposition in Healthy Aging and Synucleinopathies

AIMS: To investigate the gradients of nigrostriatal iron deposition in aging, Parkinson's disease (PD), and multiple system atrophy (MSA). METHODS: This study included 100 young healthy controls, 171 old healthy controls (OHC), 231 PD, and 24 MSA patients. The brain iron content was quantified by quantitative susceptibility mapping. A spatial function method was employed to map the iron gradient along the principal axis of the subcortical structure. General linear models were used to compare differences in iron gradients between groups. Partial correlation was used to analyze the relationship between iron content and symptoms of synucleinopathies. RESULTS: Nigrostriatal iron deposition in all gradient directions was observed during aging (p < 0.05). Compared to OHC, iron deposition was significant in nearly all substantia nigra (SN) segments in both PD and MSA (p < 0.05). MSA showed significant iron deposition in the posterolateral putamen compared to PD (p < 0.05). Iron deposition in the SN in PD and putamen in MSA correlated with disease severity. CONCLUSION: Iron deposition in all gradient directions occurred in the nigrostriatal system during healthy aging, and this was more evident in the SN in both PD and MSA, with MSA displaying additional iron deposition in the posterolateral putamen.