title: Huntington's disease - neuropathology.
abstract: An expansion of a trinucleotide CAG repeat on chromosome 4 causes Huntington disease. The abnormal elongation of the CAG increases the polyglutamine stretch of huntingtin, which becomes proportionally toxic. The mutated huntingtin is ubiquitous in somatic tissues, yet the pathologic changes are apparently restricted to the brain. The degree of the abnormal expansion of the CAG repeats governs the gradually diffuse atrophy of the brain. However, the brunt of the degenerative process involves the striatum. The onset of symptoms is insidious, but the longer the CAG expansion, the earlier their occurrence. They include psychiatric, motor, and cognitive disorders. Patients with adult onset of symptoms are more prone to exhibit choreic movements whereas those with juvenile onset tend to develop parkinsonism or rigidity. Brains from patients with juvenile onset are usually more atrophic than those with adult onset. Brains from patients with late onset of symptoms might show changes occurring in usual aging in addition to those characteristically observed in Huntington disease. Despite recent important discoveries, the pathogenesis of Huntington disease is still not elucidated. Many possible mechanisms underlying the relative selective vulnerability of neurons are being explored. In particular, factors promoting apoptosis, and phenomena causing the toxic aggregation of proteins, or the blockage of trophic factors, or mitochondria dysfunction, and excitoxicity have been studied.
authors.affiliation: Department of Pathology, Presbyterian Hospital and Columbia University, New York, NY 10032, USA. jgv2001@columbia.edu
authors.forename: Jean Paul G
authors.initials: JP
authors.lastname: Vonsattel
authors.forename: Christian
authors.initials: C
authors.lastname: Keller
authors.forename: Etty Paola
authors.initials: EP
authors.lastname: Cortes Ramirez
mesh_terms: D001479:Basal Ganglia / Q000473:pathology*; D049672:History, 19th Century; D006801:Humans; D006816:Huntington Disease / Q000235:genetics / Q000266:history / Q000473:pathology*; D018911:Trinucleotide Repeats / Q000235:genetics