Background: Aberrant accumulation of transition metals in the brain may have an early and important role in the pathogenesis of several neurodegenerative disorders, including Huntington disease (HD). Objective: To comprehensively evaluate and validate the distribution of metal deposition in the brain using advanced magnetic resonance imaging methods from the premanifest through symptomatic stages of HD. Design: Observational study. Setting: University imaging center. Participants: Twenty-eight HD expanded gene carriers, 34 patients with symptomatic HD, and 56 age- and sex-matched healthy control subjects were included in the study. Interventions: Participants underwent magnetic resonance imaging for the quantification of the phase evolution of susceptibility-weighted images. Main Outcome Measures: To verify the identity of the metals responsible for the changes in the phase evolution of the susceptibility signal in the brain and to assess correlations with systemic levels. Inductively coupled plasma mass spectrometry was used to measure transition metal concentrations in postmortem brains. Results: In the basal ganglia, progressive increases in the phase evolution were found in HD, beginning in premanifest individuals who were far from expected onset and increasing with proximity to expected onset and thereafter. Increases in the cerebral cortex were regionally selective and present only in symptomatic HD. Increases were verified by excessive deposition of brain iron, but a complex alteration in other transition metals was found. Conclusion: An important and early role of altered metal homeostasis is suggested in the pathogenesis of HD.
ASJC Scopus subject areas
- Arts and Humanities (miscellaneous)
- Clinical Neurology