Selective neurodegeneration, neuropathology and symptom profiles in Huntington's disease

Adv Exp Med Biol. 2012:769:141-52. doi: 10.1007/978-1-4614-5434-2_9.

Abstract

Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disease caused by a CAG repeat expansion in exon 1 of the Huntington gene (HD) also known as IT15. Despite the disease being caused by dysfunction ofa single gene, expressed as an expanded polyglutamine in the huntingtin protein, there is a major variability in the symptom profile of patients with Huntington's disease as well as great variability in the neuropathology. The symptoms vary throughout the course of the disease and vary greatly between cases. These symptoms present as varying degrees of involuntary movements, mood, personality changes, cognitive changes and dementia. To determine whether there is a morphological basis for this symptom variability, recent studies have investigated the cellular and neurochemical changes in the striatum and cerebral cortex in the human brain to determine whether there is a link between the pathology in these regions and the symptomatology shown by individual cases. These studies together revealed that cases showing mainly mood symptom profiles correlated with marked degeneration in the striosomal compartment of the striatum, or in the anterior cingulate gyrus of the cerebral cortex. In contrast, in cases with mainly motor symptoms neurodegeneration was especially marked in the primary motor cortex with variable degeneration in both the striosomes and matrix compartments of the striatum. These studies suggest that the variable degeneration of the striatum and cerebral cortex correlates with the variable profiles of Huntington's disease.

Publication types

  • Review

MeSH terms

  • Affect / classification
  • Brain Mapping
  • Corpus Striatum / metabolism
  • Corpus Striatum / pathology
  • Corpus Striatum / physiopathology*
  • Genetic Variation
  • Gyrus Cinguli / metabolism
  • Gyrus Cinguli / pathology
  • Gyrus Cinguli / physiopathology*
  • Humans
  • Huntingtin Protein
  • Huntington Disease / genetics*
  • Huntington Disease / pathology
  • Huntington Disease / physiopathology*
  • Motor Cortex / metabolism
  • Motor Cortex / pathology
  • Motor Cortex / physiopathology*
  • Nerve Tissue Proteins / genetics*
  • Peptides / genetics
  • Severity of Illness Index
  • Trinucleotide Repeat Expansion*

Substances

  • HTT protein, human
  • Huntingtin Protein
  • Nerve Tissue Proteins
  • Peptides
  • polyglutamine