Matrix metalloproteinase 3 haplotypes and dementia and Alzheimerʹs disease: The Rotterdam Study

Evidence by post-mortem and animal studies suggests that matrix metalloproteinases (MMPs) may play an important role in the pathophysiology of Alzheimerʹs disease (AD) through degradation of amyloid beta. We investigated in 5999 elderly whether MMP3-haplotypes are associated with cognitive performance over time, dementia and AD. We also explored the association of MMP-3 haplotypes with changes in hippocampal volume and severity of periventricular and subcortical white matter lesions (WML). There was no association between any individual polymorphism or MMP-3 haplotypes and performance in MMSE over time, dementia or AD, and there was no association between MMP-3 genotypes or haplotypes with hippocampal volume or severity of periventricular or subcortical WML. These associations did not differ between strata of APOE 4 genotype. Our observations do not suggest that variation in the MMP3 gene is causally involved in dementia or AD.