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Profiles of matrix metalloproteinases and their inhibitors in plasma of patients with dementia

Published online by Cambridge University Press:  01 February 2008

Stefan Lorenzl ,
Katharina Büerger ,
Harald Hampel  and
M. Flint Beal
Stefan Lorenzl*
Affiliation:
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, U.S.A. Department of Neurology, University of Munich, Klinikum Großhadern, Munich, Germany
Katharina Büerger
Affiliation:
Alzheimer Memorial Center and Geriatric Psychiatry Branch, Dementia Research Section, Department of Psychiatry, Ludwig-Maximilian University, Munich, Germany
Harald Hampel
Affiliation:
Alzheimer Memorial Center and Geriatric Psychiatry Branch, Dementia Research Section, Department of Psychiatry, Ludwig-Maximilian University, Munich, Germany
M. Flint Beal
Affiliation:
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, U.S.A.
*
Correspondence should be addressed to: Dr. S. Lorenzl, Dept. of Neurology, Klinikum Grosshadern, University of Munich, Marchioninistr. 15, 81377 Munich, Germany. Phone: +49 89 7095 3144; Fax: +49 89 7095 3677. Email: [email protected].
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Abstract

Background: Matrix metalloproteinases (MMPs) are elevated in the brain tissue of patients with dementia and may play a role in the pathophysiology of dementia. MMP-9 and tissue inhibitors of MMPs (TIMPs) are elevated in postmortem brain tissue of patients with Alzheimer's disease (AD). In a previous study we showed that circulating levels of MMP-9 are elevated in AD patients. The aim of the present study was to examine circulating levels of MMP-1, MMP-2, MMP-9, TIMP-1 and TIMP-2 in the plasma of patients with mild cognitive impairment (MCI), AD, vascular dementia (VaD), dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD), to determine, whether plasma profiles of MMPs and TIMPs differ in various types of dementia.

Methods: Gelatinolytic activity (MMP-2 and MMP-9) was measured in all plasma samples by zymography. Levels of MMP-2, MMP-9, MMP-1 as well as TIMP-1 and TIMP-2 were measured by ELISA.

Results: We found constitutive expression of MMP-1, -2 and -9 as well as TIMP-1 and -2 in all the samples investigated. As shown previously, MMP-9 was significantly elevated in the plasma of AD patients (p = 0.004) as compared to controls and MCI patients. Plasma levels of TIMP-1 were significantly lower in VD samples as compared to all other groups. Levels of TIMP-2 were significantly lower in patients with FTD as compared to AD, VaD and MCI patients. There were no significant changes of MMP-1 and MMP-2 levels in the samples.

Conclusion: These findings suggest that circulating levels of MMP-9, TIMP-1 and TIMP-2 and changes in the MMP/TIMP balance in plasma differ in various types of dementia.

Keywords

matrix metalloproteasesplasmaAlzheimer's diseasemild cognitive impairmentvascular dementiadementia with Lewy bodiesfrontotemporal dementia
Type
MCI CONFERENCE PAPER
Information
International Psychogeriatrics , Volume 20 , Issue 1 , February 2008 , pp. 67 - 76
Copyright
Copyright © International Psychogeriatric Association 2007

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