Iron deposits in brain disorders

Summary

Abnormal iron deposition in the CNS may be related to exogenous or endogenous factors. CNS is involved in idiopathic hemochromatosis, an autosomal recessively inherited storage disorder with increased resorption of iron in the gut. In superficial siderosis of the CNS resulting from repeated cerebral or subarachnoid bleeding, deposition of hemosiderin depends on accumulation of ferritin in the microglia. In experimental models, storage of heme-iron is mediated by shifts in the H/L ratio of ferritin. Tissue destruction is caused by Fe-catalyzed lipid peroxidation. Incrustation of neurons in perinatal brain injury or mitochondrial encephalopathies shows the presence of iron and calcium, also present in vascular deposits in basal ganglia and cerebellum in Fahr’s disease, often related to hypoparathyroidism, hemochromatosis, and mitochondrial disorders. Iron deposition in the brain is found in various neurodegenerative disorders. In Hallervorden-Spatz disease, the globus pallidus and reticulata nigrae show iron-pigment deposits associated with axonals spheroids, increased iron content and uptake in the basal ganglia demonstrated in vivo by high-field MRI and PET. Decreased cystein dioxygenase in pallidum may result in accumulation of cystein that may locally bind iron and, via lipid peroxidation, may cause neuronal damage. In striatonigral degeneration, the putamen contains lipofuscin-like pigment with 4-fold increase in iron content suggesting pigment formation via lipid peroxidation. In Parkinson’s disease, the damaged substantia nigra zona compacta shows increase of total iron and Fe³⁺, mainly in neuromelanin, suggesting that ironmelanin interaction may be a pathogenic factor, while ferritin-reactive microglia indicates active degeneration. The pathogenic role of iron increased in neurofibrillary tangles in Alzheimer’s disease needs further elucidation.