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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: Stefan.Lorenzl@med.uni-muenchen.de.
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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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References

Adair, J. C. et al. 2004. Measurement of gelatinase B (MMP-9) in the cerebrospinal fluid of patients with vascular dementia and Alzheimer disease. Stroke, 35, 159–162. DOI: 10.1161/01.STR.0000127420.10990.76Google Scholar
Asahina, M., Yoshiyama, Y. and Hattori, T. 2001. Expression of matrix metalloproteinase-9 and urinary-type plasminogen activator in Alzheimer's disease brain. Clinical Neuropathology, 20, 60–63.Google ScholarPubMed
Backstrom, J. R., Lim, G. P., Cullen, M. J. and Tokes, Z. A. 1996. Matrix metalloproteinase-9 (MMP-9) is synthesized in neurons of the human hippocampus and is capable of degrading the amyloid-beta peptide (1–40). Journal of Neuroscience, 16, 7910–7919.CrossRefGoogle ScholarPubMed
Brew, K., Dinakarpandian, D. and Nagase, H. 2000. Tissue inhibitors of metalloproteinases: evolution, structure and function. Biochimica et Biophysica Acta, 1477, 267–283. DOI: 10.1016/S0167-4838(99)00279-4.Google Scholar
Frank, R. A. et al. 2003. Biological markers for therapeutic trials in Alzheimer's disease. Proceedings of the biological markers working group; NIA initiative on neuroimaging in Alzheimer's disease. Neurobiology of Aging, 24: 521–536. DOI: 10.1016/S0197-4580(03)00002-2.CrossRefGoogle Scholar
Hampel, H. et al. 2004a. Measurement of phosphorylated tau epitopes in the differential diagnosis of Alzheimer's disease – a comparative CSF study. Archives of General Psychiatry, 61, 95–102.CrossRefGoogle Scholar
Hampel, H. et al. 2004b. Core biological marker candidates of Alzheimer's disease – perspectives for diagnosis, prediction of outcome and reflection of biological activity. Journal of Neural Transmission, 111, 247–272. DOI: 10.1007/s00702-003-0065-z.Google Scholar
Helbecque, N., Hermant, X., Cottel, D. and Amouyel, P. 2003. The role of matrix metalloproteinase-9 in dementia. Neuroscience Letters, 350, 181–183.Google Scholar
Itoh, Y., Ito, A., Iwata, K., Tanzawa, K., Mori, Y. and Nagase, H. 1998. Plasma membrane-bound tissue inhibitor of metalloproteinases (TIMP)-2 specifically inhibits matrix metalloproteinase 2 (gelatinase A) activated on the cell surface. Biological Chemistry, 273, 24360–24367.CrossRefGoogle ScholarPubMed
LaFleur, M. A., Tester, A. M. and Thompson, E. W. 2003. Selective involvement of TIMP-2 in the second activational cleavage of pro-MMP-2: refinement of the pro-MMP-2 activation mechanism. FEBS Letters, 553, 457–463. DOI: 10.1016/S0014-5793(03)01094-9.Google Scholar
Leake, A., Morris, C. M. and Whateley, J. 2000. Brain matrix metalloproteinase 1 levels are elevated in Alzheimer's disease. Neuroscience Letters, 291, 201–203. DOI: 10.1016/S0304-3940(00)01418-X.Google Scholar
Lee, M. A., Palace, J., Stabler, G., Ford, J., Gearing, A. and Miller, K. 1999. Serum gelatinase B, TIMP-1 and TIMP-2 levels in multiple sclerosis. A longitudinal clinical and MRI study. Brain, 122, 191–197.CrossRefGoogle ScholarPubMed
Lorenzl, S. et al. 2003. Increased plasma levels of matrix metalloproteinase-9 in patients with Alzheimer's disease. Neurochemistry International, 43, 191–196. DOI: 10.1016/S0197-0186(03)00004-4.CrossRefGoogle ScholarPubMed
Lund and Manchester Groups 1994. Clinical and neuropathological criteria for frontotemporal dementia. Journal of Neurology, Neurosurgery, and Psychiatry, 57, 416–418.CrossRefGoogle Scholar
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D. and Stadlan, E. M. 1984. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology, 34, 939–944.Google Scholar
McKeith, I. G. et al. 2000. Prospective validation of consensus criteria for the diagnosis of dementia with Lewy bodies. Neurology, 54, 1050–1058.CrossRefGoogle ScholarPubMed
Morris, J. C. et al. 1989. The consortium to establish a registry for Alzheimer's disease (CERAD). Part I. Clinical and neuropsychological assessment of Alzheimer's disease. Neurology, 39, 1159–1165.Google Scholar
Peress, N., Perillo, E. and Zucker, S. 1995. Localization of tissue inhibitor of matrix metalloproteinases in Alzheimer's disease and normal brain. Journal of Neuropathology and Experimental Neurology, 54, 16–22.CrossRefGoogle ScholarPubMed
Petersen, R. C., Smith, G. E., Waring, S. C., Ivnik, R. J., Tangalos, E. G. and Kokmen, E. 1999. Mild cognitive impairment: clinical characterization and outcome. Archives of Neurology, 56, 303–308.CrossRefGoogle ScholarPubMed
Pratico, D., Clark, C. M., Liun, F., Rokach, J., Lee, V. Y. and Trojanowski, J. Q. 2002. Increase of brain oxidative stress in mild cognitive impairment: a possible predictor of Alzheimer disease. Archives of Neurology, 59, 972–976.CrossRefGoogle ScholarPubMed
Rinaldi, P. et al. 2003. Plasma antioxidants are similary depleted in mild cognitive impairment and in Alzheimer's disease. Neurobiology of Aging, 24, 915–917. DOI: 10.1016/S0197-4580(03)00031-9Google Scholar
Rosenberg, G. A., Sullivan, N. and Esiri, M. M. 2001. White matter damage is associated with matrix metalloproteinases in vascular dementia. Stroke, 32, 1162–1168.CrossRefGoogle ScholarPubMed
Sayre, L. M., Smith, M.A. and Perry, G. 2001. Chemistry and biochemistry of oxidative stress in neurodegenerative disease. Current Medical Chemistry, 8, 721–738.CrossRefGoogle ScholarPubMed
Scheuner, D. et al. 1996. Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease. Nature Medicine, 2, 864–870.CrossRefGoogle ScholarPubMed
Stix, B., Kahne, T., Sletten, K., Raynes, J., Roessner, A. and Rocken, C. 2001. Proteolysis of AA amyloid fibrils by matrix metalloproteinases-1, -2, and -3. American Journal of Pathology, 159, 561–570.Google Scholar
Vincenti, M. P. 2001. The matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) genes. Transcriptional and posttranscriptional regulation, signal transduction and cell-type-specific expression. Methods in Molecular Biology, 151, 121–148.Google Scholar
Yan, P. et al. 2006. Matrix metalloproteinase-9 degrades amyloid-beta fibrils in vitro and compact plaques in situ. Journal of Biological Chemistry, 281, 24566–24574. DOI: 10.1074/jbc.M602440200.Google Scholar