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Matrix metalloproteinases in peripheral blood and cerebrospinal fluid in patients with Alzheimer's disease

Published online by Cambridge University Press:  18 June 2010

Solveig Horstmann ,
Leila Budig ,
Humphrey Gardner ,
James Koziol ,
Michael Deuschle ,
Claudia Schilling  and
Simone Wagner
Solveig Horstmann
Affiliation:
Department of Neurology, Medical School, University of Heidelberg, Heidelberg, Germany
Leila Budig
Affiliation:
Department of Neurology, Medical School, University of Heidelberg, Heidelberg, Germany
Humphrey Gardner
Affiliation:
Novartis, Cambridge, MA, USA
James Koziol
Affiliation:
Scripps Research Institute, La Jolla, CA, U.S.A.
Michael Deuschle
Affiliation:
Central Institute of Mental Health, Mannheim, Germany
Claudia Schilling
Affiliation:
Central Institute of Mental Health, Mannheim, Germany
Simone Wagner*
Affiliation:
Department of Neurology, Medical School, University of Heidelberg, Heidelberg, Germany
*
Correspondence should be addressed to: Simone Wagner, Department of Neurology, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany. Phone: +49-6221-567504; Fax: +49-6221-565461. Email: simone.wagner@med.uni-heidelberg.de.
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Abstract

Background: Deposition of amyloid β 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 β, 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.

Keywords

matrix metalloproteinasesAlzheimer's diseasedementia
Type
Research Article
Information
International Psychogeriatrics , Volume 22 , Special Issue 6: Focus on training in psychogeriatrics , September 2010 , pp. 966 - 972
Copyright
Copyright © International Psychogeriatric Association 2010

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