Is there a genetic basis for the deposition of β-amyloid after fatal head injury?

被引:21
作者
Graham, DI
Gentleman, SM
Nicoll, JAR
Royston, MC
McKenzie, JE
Roberts, GW
Mrak, RE
Griffin, WST
机构
[1] Univ Glasgow, Dept Neuropathol, Glasgow, Lanark, Scotland
[2] Charing Cross & Westminster Med Sch, Dept Anat, London W6 8RF, England
[3] Charing Cross & Westminster Med Sch, Dept Psychiat, London W6 8RF, England
[4] SmithKline Beecham, Dept Mol Neuropathol, Harlow, Essex, England
[5] Arkansas Childrens Hosp, Inst Res, Dept Neuropathol & Paediat & Anat, Little Rock, AR 72202 USA
关键词
head injury; beta-APP metabolism; beta-amyloid; apolipoprotein E;
D O I
10.1023/A:1006937205905
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
1. Alzheimer's disease is a heterogeneous disorder that may be caused by genetic or environmental factors or by a combination of both. Abnormalities in chromosomes 1, 14, and 21 have all been implicated in the pathogenesis of the early-onset form of the disease, while the epsilon 3 allele of the apolipoprotein E gene (on chromosome 19) is nov: recognized as a risk factor for early- and late-onset sporadic and familial Alzheimer's disease. 2. The best-established environmental trigger for the disease is a head injury, based on epidemiological and neuropathological evidence. Approximately 30% of patients who die after a single episode of severe head injury show intracerebral deposition of beta-amyloid protein (A beta), a protein that is thought to be central to the pathogenesis of Alzheimer's disease. 3. Recent studies have revealed an over-representation of the apoE epsilon 4 allele in those head-injured patients displaying A beta pathology, thus providing the first evidence for a link between a genetic susceptibility (apoE epsilon 4) and an environmental trigger (head injury) in the development of Alzheimer-type pathology.
引用
收藏
页码:19 / 30
页数:12
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