In this first application of Quantitative Susceptibility Mapping Source Separation to cerebral adrenoleukodystrophy, we uncovered alterations in iron and myelin within lesions and normal appearing white matter. As validation, we demonstrate abnormal iron accumulation in those same compartments within primary brain tissue. A gradient of microglial activation to absence parallels the transition from normal white matter to demyelinated lesion. In perilesional white matter, increases in myelin peroxidation and Acyl-CoA synthetase long-chain family member 4 are observed. Thus, the unifying mechanistic relationship of apoptosis to lipid peroxidation in the presence of iron implicates ferroptosis in the pathogenesis of cerebral adrenoleukodystrophy.
Nemeth et al. (Tue,) studied this question.