Book contents
- Frontmatter
- Contents
- List of contributors
- List of abbreviations
- Preface to second edition
- 1 Definition, clinical features and neuroanatomical basis of dementia
- 2 Important anatomical landmarks in the brain in dementia
- 3 Practical approach to pathological diagnosis
- 4 Morphometric methods and dementia
- 5 Safety precautions in laboratories involved with dementia diagnosis and research
- 6 Molecular diagnosis of dementia
- 7 Neuropathology of the ageing brain
- 8 Neuroimaging Alzheimer's disease
- 9 Alzheimer's disease
- 10 Down's syndrome and Alzheimer's disease
- 11 Sporadic tauopathies: Pick's disease, corticobasal degeneration, progressive supranuclear palsy and argyrophilic grain disease
- 12 Hereditary tauopathies and idiopathic frontotemporal dementias
- 13 Vascular dementias
- 14 Familial and sporadic cerebral amyloid angiopathies associated with dementia and the BRI dementias
- 15 Parkinson's disease, dementia with Lewy bodies, multiple system atrophy and the spectrum of diseases with α-synuclein inclusions
- 16 Huntington's disease
- 17 Human prion diseases
- 18 Alcoholism and dementia
- 19 Hydrocephalus and dementia
- 20 Head injury and dementia
- 21 Infectious (and inflammatory) diseases causing dementia
- 22 Schizophrenia and its dementia
- 23 Other diseases that cause dementia
- 24 Transgenic mouse models of neurodegenerative disease
- Appendix: Dementia brain banks
- Index
16 - Huntington's disease
Published online by Cambridge University Press: 12 October 2009
- Frontmatter
- Contents
- List of contributors
- List of abbreviations
- Preface to second edition
- 1 Definition, clinical features and neuroanatomical basis of dementia
- 2 Important anatomical landmarks in the brain in dementia
- 3 Practical approach to pathological diagnosis
- 4 Morphometric methods and dementia
- 5 Safety precautions in laboratories involved with dementia diagnosis and research
- 6 Molecular diagnosis of dementia
- 7 Neuropathology of the ageing brain
- 8 Neuroimaging Alzheimer's disease
- 9 Alzheimer's disease
- 10 Down's syndrome and Alzheimer's disease
- 11 Sporadic tauopathies: Pick's disease, corticobasal degeneration, progressive supranuclear palsy and argyrophilic grain disease
- 12 Hereditary tauopathies and idiopathic frontotemporal dementias
- 13 Vascular dementias
- 14 Familial and sporadic cerebral amyloid angiopathies associated with dementia and the BRI dementias
- 15 Parkinson's disease, dementia with Lewy bodies, multiple system atrophy and the spectrum of diseases with α-synuclein inclusions
- 16 Huntington's disease
- 17 Human prion diseases
- 18 Alcoholism and dementia
- 19 Hydrocephalus and dementia
- 20 Head injury and dementia
- 21 Infectious (and inflammatory) diseases causing dementia
- 22 Schizophrenia and its dementia
- 23 Other diseases that cause dementia
- 24 Transgenic mouse models of neurodegenerative disease
- Appendix: Dementia brain banks
- Index
Summary
Huntington's disease (HD) is an autosomal dominant illness, usually with mid-life onset, of psychiatric, cognitive and motor symptoms. Death occurs 12–15 years from the time of symptomatic onset (Folstein, 1989; Harper et al., 1991). The HD mutation consists of an unstable expansion of CAG (trinucleotide) repeats within the coding region of the gene ‘IT15’ (for ‘Interesting transcript’ referred to as HD-IT15 CAG repeats). This gene, on chromosome 4 (4p63), encodes the 350 kDa protein huntingtin of unknown function (Group et al., 1993). An expanded polyglutamine residue (polyQ) distinguishes the mutated huntingtin (with about 37 to 250 polyQ) from the wild type (with 8 to about 34–36 polyQ) (Nance et al., 1999; Rubinsztein et al., 1996). The disease occurs when the critical threshold of about 37 polyQ is exceeded. This phenomenon is observed in a group of inherited, neurodegenerative diseases caused by polyQ extension, which is increasingly referred to as polyglutaminopathies (Paulson, 1999). The pathogenicity of the mutant huntingtin is unknown. The mutant huntingtin retains some functions of the wild type huntingtin since individuals homozygous for the HD gene produce only mutant huntingtin and are clinically indistinguishable from heterozygous patients (Wexler et al., 1987; Myers et al., 1989). The mutant huntingtin is present in all organs, yet the brunt of the changes of HD identified so far occurs in the brain (Sathasivam et al., 1999). The degeneration involves initially the striatum (neuronal loss, gliosis) and cortex, and eventually may appear throughout the brain as a constellation of the toxic effect of the mutation and the ensuing secondary changes.
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- The Neuropathology of Dementia , pp. 376 - 401Publisher: Cambridge University PressPrint publication year: 2004
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