title: Assessment of cortical and striatal involvement in 523 Huntington disease brains.
abstract: OBJECTIVE
  To evaluate the relationship of striatal involvement in Huntington disease (HD) to involvement in other brain regions, CAG repeat size, onset age, and other factors.
  
  
  METHODS
  We examined patterns of neuropathologic involvement in 664 HD brains submitted to the Harvard Brain Tissue Resource Center. Brains with concomitant Alzheimer or Parkinson changes (n = 82), more than 20% missing data (n = 46), incomplete sample submission (n = 12), or CAG repeat less than 36 (n = 1) were excluded, leaving 523 cases. Standardized ratings from 0 (absent) to 4 (severe) of gross and microscopic involvement were performed for 50 regions. Cluster analysis reduced the data to 2 main measures of involvement: striatal and cortical.
  
  
  RESULTS
  The clusters were correlated with each other (r = 0.42) and with disease duration (striatal: r = 0.35; cortical: r = 0.31). The striatal cluster was correlated with HD repeat size (r = 0.50). The cortical cluster showed a stronger correlation with decreased brain weight (r = -0.52) than the striatal cluster (r = -0.33). The striatal cluster was correlated with younger death age (r = -0.31) and onset age (r = -0.46) while the cortical cluster was not (r = 0.09, r = -0.04, respectively).
  
  
  CONCLUSIONS
  The 2 brain clusters had different relationships to the HD CAG repeat size, onset age, and brain weight, suggesting that neuropathologic involvement does not proceed in a strictly coupled fashion. The pattern and extent of involvement varies substantially from one brain to the next. These results suggest that regional involvement in HD brain is modified by factors which, if identified, may lend insight into novel routes to therapeutics.
authors.affiliation: Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Tiffany C
authors.initials: TC
authors.lastname: Hadzi
authors.forename: Audrey E
authors.initials: AE
authors.lastname: Hendricks
authors.forename: Jeanne C
authors.initials: JC
authors.lastname: Latourelle
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Lunetta
authors.forename: L Adrienne
authors.initials: LA
authors.lastname: Cupples
authors.forename: Tammy
authors.initials: T
authors.lastname: Gillis
authors.forename: Jayalakshmi Srinidhi
authors.initials: JS
authors.lastname: Mysore
authors.forename: James F
authors.initials: JF
authors.lastname: Gusella
authors.forename: Marcy E
authors.initials: ME
authors.lastname: MacDonald
authors.forename: Richard H
authors.initials: RH
authors.lastname: Myers
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Vonsattel
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D001344:Autopsy; D001921:Brain / Q000473:pathology; D002102:Cadaver; D002421:Caudate Nucleus / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology*; D016000:Cluster Analysis; D005260:Female; D005911:Gliosis / Q000473:pathology; D006801:Humans; D006816:Huntington Disease / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D017072:Neostriatum / Q000473:pathology*; D009474:Neurons / Q000473:pathology; D009929:Organ Size; D018911:Trinucleotide Repeats