Neurobiology of Aging
Volume 28, Issue 8 , Pages 1215-1220, August 2007

Impact of the matrix metalloproteinase MMP-3 on dementia

  • Nicole Helbecque

      Affiliations

    • INSERM U744, Institut Pasteur de Lille, 1 rue du Professeur Calmette, BP245, 59019 Lille Cedex, France
    • ,
  • Dominique Cottel

      Affiliations

    • INSERM U744, Institut Pasteur de Lille, 1 rue du Professeur Calmette, BP245, 59019 Lille Cedex, France
    • ,
  • Xavier Hermant

      Affiliations

    • INSERM U744, Institut Pasteur de Lille, 1 rue du Professeur Calmette, BP245, 59019 Lille Cedex, France
    • ,
  • Philippe Amouyel

      Affiliations

    • INSERM U744, Institut Pasteur de Lille, 1 rue du Professeur Calmette, BP245, 59019 Lille Cedex, France
    • Université de Lille 2, CHRU de Lille, Place de Verdun, Lille, France
    • Corresponding Author InformationCorresponding author. Tel.: +33 3 20 87 77 10; fax: +33 3 20 87 78 94.

Received 14 December 2005; received in revised form 24 May 2006; accepted 29 May 2006. published online 07 July 2006.

Abstract 

Cerebral accumulation of β-amyloid peptide (Aβ) is a central event in the pathogenesis of Alzheimer's disease (AD). Several proteases were shown to hydrolyze Aβ in vitro or in cell-based assays, and are likely candidates for a role in Aβ 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 ɛ4 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.

Keywords: Alzheimer's disease, Late-onset Alzheimer's disease, β-Amyloid peptide, Clearance, Matrix metalloproteinase, Genetic polymorphism, Genetic association study

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PII: S0197-4580(06)00189-8

doi:10.1016/j.neurobiolaging.2006.05.030

Neurobiology of Aging
Volume 28, Issue 8 , Pages 1215-1220, August 2007

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