title: Alterations in brain transition metals in Huntington disease: an evolving and intricate story.
abstract: 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.
  
  
  METHODS
  Observational study.
  
  
  METHODS
  University imaging center.
  
  
  METHODS
  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.
  
  
  METHODS
  Participants underwent magnetic resonance imaging for the quantification of the phase evolution of susceptibility-weighted images.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  An important and early role of altered metal homeostasis is suggested in the pathogenesis of HD.
authors.affiliation: Department of Neurology, Center for Neuroimaging of Aging and Neurodegenerative Diseases, Massachusetts General Hospital, Charlestown, 02129, USA. rosas@helix.mgh.harvard.edu
authors.forename: H Diana
authors.initials: HD
authors.lastname: Rosas
authors.forename: Y Iris
authors.initials: YI
authors.lastname: Chen
authors.forename: Gheorghe
authors.initials: G
authors.lastname: Doros
authors.forename: David H
authors.initials: DH
authors.lastname: Salat
authors.forename: Nan-kuei
authors.initials: NK
authors.lastname: Chen
authors.forename: Ken K
authors.initials: KK
authors.lastname: Kwong
authors.forename: Ashley
authors.initials: A
authors.lastname: Bush
authors.forename: Jonathan
authors.initials: J
authors.lastname: Fox
authors.forename: Steven M
authors.initials: SM
authors.lastname: Hersch
mesh_terms: D000328:Adult; D001921:Brain / Q000378:metabolism*; D001931:Brain Mapping; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D021621:Imaging, Three-Dimensional; D007501:Iron / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D019370:Observation; D012720:Severity of Illness Index
chemical_list: D007501:Iron