Impact of the matrix metalloproteinase MMP-3 on dementia

被引:20
|
作者
Helbecque, Nicole
Cottel, Dominique
Hermant, Xavier
Amouyel, Philippe
机构
[1] Inst Pasteur Lille 1, INSERM, U744, F-59019 Lille, France
[2] Univ Lille 2, CHRU Lille, Lille, France
关键词
Alzheimer's disease; late-onset Alzheimer's disease; beta-amyloid peptide; clearance; matrix metalloproteinase; genetic polymorphism; genetic association study;
D O I
10.1016/j.neurobiolaging.2006.05.030
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
Cerebral accumulation of P-amyloid peptide (A beta) is a central event in the pathogenesis of Alzheimer's disease (AD). Several proteases were shown to hydrolyze A beta in vitro or in cell-based assays, and are likely candidates for a role in A beta clearance in brain. Previous reports suggest that matrix metalloproteinases (MMPs) could be involved in such a mechanism. A functional polymorphism at position - 1171 (5A/6A) in MMP-3 was examined in two independent studies to investigate the impact of this polymorphism on the risk of developing dementia. We found that subjects APOE epsilon 4 non-carriers and 6A/6A homozygous for the MMP-3 polymorphism were at increased risk of dementia. Our findings support the hypothesis that MMPs may influence the risk of dementia. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:1215 / 1220
页数:6
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