Impact of the matrix metalloproteinase MMP-3 on dementia.
Cerebral accumulation of beta-amyloid peptide (Abeta) is a central event in the pathogenesis of Alzheimer's disease (AD). Several proteases were shown to hydrolyze Abeta in vitro or in cell-based assays, and are likely candidates for a role in Abeta 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 epsilon4 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.
Helbecque
Nicole
N
INSERM U744, Institut Pasteur de Lille, Lille Cedex, France.
Cottel
Dominique
D
Hermant
Xavier
X
Amouyel
Philippe
P
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000201:enzymology / Q000235:genetics; D053327:Apolipoprotein E4 / Q000235:genetics; D004252:DNA Mutational Analysis; D003704:Dementia / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D012306:Risk
D053327:Apolipoprotein E4; D019278:Matrix Metalloproteinase 3