Increased plasma levels of matrix metalloproteinase-9 in patients with Alzheimer's disease.
Matrix metalloproteinases (MMPs) may play a role in the pathophysiology of Alzheimer's disease (AD). MMP-9 and tissue inhibitors of metalloproteinases (TIMPs) are elevated in postmortem brain tissue of AD patients. MMPs and TIMPs are found in neurons, microglia, vascular endothelial cells and leukocytes. The aim of this study was to determine whether circulating levels of MMP-2, MMP-9, TIMP-1 and TIMP-2 are elevated in the plasma of AD patients. We compared AD patients to age- and gender-matched controls as well as to Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS) patients. There was constitutive expression of gelatinase A (MMP-2), and gelatinase B (MMP-9), in all the samples as shown by zymographic analysis. Levels of MMP-9 were significantly (P=0.003) elevated in the plasma of AD patients as compared to controls. Plasma levels of MMP-2, TIMP-1 and TIMP-2 were unchanged. There were no significant changes of MMP-2, MMP-9, TIMP-1 and TIMP-2 levels in PD and ALS samples. TIMP-1 and TIMP-2 were significantly correlated with MMP-9 in the AD patients. ApoE genotyping of plasma samples showed that levels of MMP-2, TIMP-1 and TIMP-2 and MMP-9 were not significantly different between the ApoE subgroups. These findings indicate that circulating levels of MMP-9 are increased in AD and may contribute to disease pathology.
Lorenzl
Stefan
S
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 525 East 68th Street, Room F-610, New York, NY 10021, USA.
Albers
David S
DS
Relkin
Norman
N
Ngyuen
Terry
T
Hilgenberg
Sarah L
SL
Chirichigno
Jason
J
Cudkowicz
Merit E
ME
Beal
M Flint
MF
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000196:embryology*; D001057:Apolipoproteins E / Q000235:genetics; D015153:Blotting, Western; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged
D001057:Apolipoproteins E; D020780:Matrix Metalloproteinase 9