The role of iron imaging in Huntington's disease

Huntington's disease (HD) is a devastating neurological disorder that affects the brain. The cause of HD is an expanded CAG trinucleotide repeat in the Htt gene. The Htt gene is responsible for the protein huntingtin, the exact functions of which have yet to be elucidated. The role of iron in the pathological cascade is usually mentioned in the context of an inability to regulate iron homeostasis, which generates a surplus of reactive iron and free radical toxicity, resulting in increased oxidative stress. In this review, we discuss the role of iron within the existing hypotheses of HD pathology, ex vivo findings in support of increased iron in HD, and finally in vivo MRI findings in manifest and premanifest HD. Both in vivo and ex vivo findings support the notion that excess iron is present in the brain of HD patients. There does not seem to be much evidence that iron accumulation is the initiator of the pathological cascade as little or no evidence can be found for very early increased iron in the HD brain, when neuronal cell loss is already extensive.