Neurofibrillary tangles and senile plaques, constituted of extracellular amyloid deposits (Abeta), are the two defining pathological hallmarks of Alzheimer's disease (AD). Inhibiting the synthesis or aggregation of Abeta or increasing its clearance may reduce the detrimental effects of this peptide and consequently improve cognitive functions in patients. Previous studies indicated that metalloproteinases are involved in Abeta degradation and the presence of matrix metalloproteinases (MMP) in AD plaques has been described. In this study, we examined the distribution of a functional polymorphism in the gene for MMP-9, -1562 C-->T, in an independent population of 229 demented and 253 control individuals. We observed a weak protective effect of the high activity allele (T) in apolipoprotein E epsilon4 allele non-bearers (odds ratio=0.5 (95% confidence interval, 0.3-0.9), P=0.04).