Nigrostriatal iron accumulation in the progression of Parkinson’s disease

Abstract

Iron deposition in the nigrostriatal system plays a pivotal role in Parkinson’s disease (PD) onset and progression. This study explored the time course of nigrostriatal iron accumulation in 54 PD patients at early to moderately advanced stages and 20 age-matched healthy controls. Using multi-echo T2*-MRI and R2* relaxometry, iron content was assessed in the substantia nigra pars compacta (SNpc) and striatum. In vivo findings were contrasted with histological analyses in a progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism model involving six non-human primates (NHPs) and two controls using Perls’ Prussian blue staining. Complementarily, dopaminergic degeneration was quantified by 6-[¹⁸F]-fluoro-L-dopa PET in humans and TH immunohistochemistry in NHPs. Results showed progressive iron accumulation in the SNpc correlating with striatal dopaminergic denervation and neuronal loss. Striatal iron followed a V-shaped progression, decreasing initially and increasing later. Iron in the SNpc may serve as a marker of neurodegeneration in PD, while decreased striatal iron may indicate pathological susceptibility to dopaminergic loss.