MMP-2, -3 and -9 levels and activity are not related to Abeta load in the frontal cortex in Alzheimer's disease.
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.
Baig
S
S
Dementia Research Group, Institute of Clinical Neurosciences, Department of Clinical Science at North Bristol, University of Bristol, Frenchay Hospital, Bristol, UK.
Kehoe
P G
PG
Love
S
S
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
D016229:Amyloid beta-Peptides; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9