Matrix metalloproteinases in peripheral blood and cerebrospinal fluid in patients with Alzheimer's disease.
BACKGROUND
Deposition of amyloid beta in senile plaques and in cerebral blood vessels is one hallmark of the pathogenesis of Alzheimer's disease (AD). The ability of several matrix metalloproteinases (MMPs) to degrade amyloid precursor protein leading to aggregation of amyloid beta, as well as the increased expression of MMPs in post mortem brain tissue of Alzheimer's patients, indicate that MMPs play an important role in the pathogenesis of AD.


METHODS
We investigated levels of MMP-2,-3,-9 and -10 in plasma and cerebrospinal fluid (CSF) of AD patients (n = 14) by gelatin and casein zymography. Comparisons between AD patients and controls relative to levels of MMP-2, MMP-3, MMP-9, and MMP-10 were made with Wilcoxon rank statistics. Pearson correlations were computed as measures of association.


RESULTS
MMP-3 in AD was significantly elevated in plasma (p = 0.006) and there was a trend towards increase in CSF (p = 0.05). MMP-2 in CSF of AD patients was significantly decreased (p = 0.02) while levels in plasma remained unchanged. MMP-9 and MMP-10 could not be detected in CSF; MMP-10 was unchanged in plasma, but MMP-9 was significantly decreased (p = 0.02).


CONCLUSIONS
These findings constitute further evidence for the important role of MMPs in the pathogenesis of AD.
Horstmann
Solveig
S
Department of Neurology, Medical School, University of Heidelberg, Heidelberg, Germany.
Budig
Leila
L
Gardner
Humphrey
H
Koziol
James
J
Deuschle
Michael
M
Schilling
Claudia
C
Wagner
Simone
S
D000368:Aged; D000544:Alzheimer Disease / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016657:Cerebral Amyloid Angiopathy / Q000503:physiopathology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D053506:Matrix Metalloproteinase 10 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008609:Mental Status Schedule; D008875:Middle Aged; D012016:Reference Values
D016229:Amyloid beta-Peptides; D020782:Matrix Metalloproteinases; D019278:Matrix Metalloproteinase 3; D053506:Matrix Metalloproteinase 10; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1