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


CONCLUSIONS
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.
Lorenzl
Stefan
S
Department of Neurology and Neurosience, Weill Medical College of Cornell University, New York, USA. Stefan.Lorenzl@med.uni-muenchen.de
Buerger
Katharina
K
Hampel
Harald
H
Beal
M Flint
MF
D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology; D003072:Cognition Disorders / Q000175:diagnosis / Q000201:enzymology*; D003704:Dementia / Q000175:diagnosis / Q000201:enzymology*; D015140:Dementia, Vascular / Q000175:diagnosis / Q000201:enzymology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D020961:Lewy Body Disease / Q000175:diagnosis / Q000201:enzymology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D020782:Matrix Metalloproteinases / Q000097:blood*; D008569:Memory Disorders / Q000175:diagnosis / Q000201:enzymology; D008875:Middle Aged; D009483:Neuropsychological Tests; D020774:Pick Disease of the Brain / Q000175:diagnosis / Q000201:enzymology; D010949:Plasma / Q000737:chemistry; D012720:Severity of Illness Index; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood; D019714:Tissue Inhibitor of Metalloproteinases / Q000097:blood*
D019715:Tissue Inhibitor of Metalloproteinase-1; D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1