title: Symptom heterogeneity in Huntington's disease correlates with neuronal degeneration in the cerebral cortex.
abstract: BACKGROUND
  Huntington's disease (HD) is characterised by variable symptoms and neuropathology of the basal ganglia and cortex. Previously, we have shown that the pattern of pyramidal cell loss in 8 different cortical regions correlates with the phenotypic variability in HD. In the primary motor and anterior cingulate cortices, the pattern of interneuron degeneration correlates with pyramidal cell death and variable HD symptom profiles.
  
  
  OBJECTIVE
  This study aimed to examine the pattern of interneuron degeneration in 3 further regions of the HD cortex (primary sensory, superior frontal, superior parietal cortices) to determine whether HD neuropathogenesis was characterised by a general fundamental pattern of cortical interneuron loss, and explore the relationship between cortical interneuron loss with previously determined pyramidal cell loss and clinical heterogeneity.
  
  
  METHODS
  Stereological counting was used to quantify 3 sub-populations of calcium-binding protein containing interneurons in 3 cortical human brain regions of 14 HD and 13 control cases as used in our previous studies (Nana et al., 2014; Kim et al., 2014). The HD cases were grouped according to their predominant symptom profile ("motor", "mood", "mixed").
  
  
  RESULTS
  The present results demonstrated a heterogeneous loss of interneurons across the 3 cortical regions which, when compared with our previous studies, mirrored the pattern of pyramidal cell loss in the same cortical areas. Most interestingly, the pattern of neuronal loss in these regions correlated with the variable HD symptom profiles.
  
  
  CONCLUSIONS
  The overall findings in our present and previous cortical studies establish a clear correlative pattern of variable cortical neuronal degeneration in HD pathogenesis, which mirrors the heterogeneity of HD symptom phenotypes.
authors: Centre for Brain Research, University of Auckland, Auckland, New Zealand; Department of Anatomy and Medical Imaging, University of Auckland, Auckland, New Zealand.
authors: Nasim F
authors: NF
authors: Mehrabi
authors: Centre for Brain Research, University of Auckland, Auckland, New Zealand; Department of Anatomy and Medical Imaging, University of Auckland, Auckland, New Zealand.
authors: Henry J
authors: HJ
authors: Waldvogel
authors: Centre for Brain Research, University of Auckland, Auckland, New Zealand; Department of Psychology, University of Auckland, Auckland, New Zealand.
authors: Lynette J
authors: LJ
authors: Tippett
authors: Centre for Brain Research, University of Auckland, Auckland, New Zealand; Department of Psychology, University of Auckland, Auckland, New Zealand.
authors: Virginia M
authors: VM
authors: Hogg
authors: Centre for Brain Research, University of Auckland, Auckland, New Zealand; Forensic Pathology, Auckland City Hospital, Auckland, New Zealand.
authors: Beth J
authors: BJ
authors: Synek
authors: Centre for Brain Research, University of Auckland, Auckland, New Zealand; Department of Anatomy and Medical Imaging, University of Auckland, Auckland, New Zealand. Electronic address: rlm.faull@auckland.ac.
authors: Richard L M
authors: RL
authors: Faull
mesh_terms: D000328:Adult; D000368:Aged; D001344:Autopsy; D016923:Cell Death; D002540:Cerebral Cortex / Q000473:pathology*; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000150:complications* / Q000235:genetics; D007395:Interneurons / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000209:etiology* / Q000473:pathology*
keywords: Cerebral cortex; Huntington's disease; Interneurons; Pathology; Pyramidal cells; Variable symptoms