MMP-2, -3 and -9 levels and activity are not related to Abeta load in the frontal cortex in Alzheimer's disease.

Abstract

Matrix metalloproteinases (MMPs) -2, -3 and -9 are up-regulated in several cell types on exposure to amyloid beta peptide (Abeta) and have Abeta-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 Abeta 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 Abeta 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 Abeta load. Our findings suggest that altered expression of these proteases does not make a significant contribution to the accumulation of Abeta in AD.

• Authors: S Baig, P G Kehoe, S Love
• Journal: Neuropathology and applied neurobiology (Neuropathol Appl Neurobiol) Vol. 34 Issue 2 Pg. 205-15 (Apr 2008) ISSN: 1365-2990 [Electronic] England
• PMID: 17971072 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Matrix Metalloproteinase 3
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9

Topics

• Aged
• Aged, 80 and over
• Alzheimer Disease (enzymology, genetics, pathology)
• Amyloid beta-Peptides (metabolism)
• Female
• Frontal Lobe (enzymology, pathology)
• Humans
• Immunohistochemistry
• Male
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 3 (genetics, metabolism)
• Matrix Metalloproteinase 9 (genetics, metabolism)
• Polymerase Chain Reaction
• Polymorphism, Genetic
• Promoter Regions, Genetic