Journal
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
Volume 34, Issue 2, Pages 205-215Publisher
BLACKWELL PUBLISHING
DOI: 10.1111/j.1365-2990.2007.00897.x
Keywords
A beta; Alzheimer's disease; gene polymorphisms; matrix metalloproteinases
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Funding
- Alzheimers Research UK [ART-EG2005B-1, ART-EG2003A-3] Funding Source: researchfish
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Matrix metalloproteinases (MMPs) -2, -3 and -9 are up-regulated in several cell types on exposure to amyloid beta peptide (A beta) and have A beta-degrading activity in vitro. The aims of this study were to determine (i) the distribution of MMP-2, -3 and -9 in the cerebral cortex in Alzheimer's disease (AD) and control brains; (ii) whether the levels and activity of these proteases are increased in AD; and (iii) whether their activity is related to A beta load. In addition, we examined whether promoter polymorphisms in the MMP-3 and -9 genes are associated with AD in the study cohort. Paraffin sections of frontal lobe from AD and control cases were immunostained for MMP-2, -3 and -9 and tissue homogenates used for MMP activity assays. DNA from these cases was genotyped for the MMP-3 5A/6A (-1171) and MMP-9 C-1562T promoter polymorphisms. Immunohistochemistry revealed MMP-3 in plaques and both MMP-3 and -9 around scattered neurones. The levels and activity of all three MMPs were similar in AD and control brains and bore no relationship to A beta load. Analysis of MMP-3 -1171 5A/6A allele frequencies showed that the 6A allele (with reduced promoter activity) was associated with AD; the MMP-9 C-1562T polymorphism was not. The levels and activities of MMP-2, -3 and -9 are not increased in the frontal cortex in AD and are not related to A beta load. Our findings suggest that altered expression of these proteases does not make a significant contribution to the accumulation of A beta in AD.
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