title: Investigation of matrix metalloproteinases, MMP-2 and MMP-9, in plasma reveals a decrease of MMP-2 in Alzheimer's disease.
abstract: Pathological changes in the Alzheimer's disease (AD) brain include amyoid-β (Aβ) plaques, and neurofibrillary tangles, as well as neuronal death and synaptic loss. Matrix metalloproteinases MMP-2 and MMP-9 are known to degrade Aβ, and their expressions are increased in the AD brain, in particular in the astrocytes surrounding amyloid plaque. To investigate a possible association between plasma metalloproteinases and AD, we quantified MMP-2 and MMP-9 activities in the plasma of healthy controls (HC, n = 56), cases with mild cognitive impairment (MCI, n = 45), and AD (n = 50). All cases had previously been imaged with Pittsburgh compound B (PiB) and had a Mini-Mental Status Examination (MMSE) assessment. MMP-2 and MMP-9 activity was determined using gelatine-zymography. There was a significant 1.5-fold decrease in MMP-2 activity in the AD group compared to HC (p < 0.001) and a 1.4-fold decrease compared to MCI (p < 0.01). There was no difference in MMP-9 levels between the three groups. A positive correlation was identified between MMP-2 plasma activity and MMSE score (r = 0.16, p < 0.05), but there was no association with PiB. This is the first report of a change in MMP-2 activity in AD plasma and these findings may provide some insight into AD pathogenesis.
authors.affiliation: Department of Pathology, The University of Melbourne, Parkville Vic, Australia.
authors.forename: Nastasia K-H
authors.initials: NK
authors.lastname: Lim
authors.forename: Victor L
authors.initials: VL
authors.lastname: Villemagne
authors.forename: Cynthia P W
authors.initials: CP
authors.lastname: Soon
authors.forename: Katrina M
authors.initials: KM
authors.lastname: Laughton
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Rowe
authors.forename: Catriona A
authors.initials: CA
authors.lastname: McLean
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.forename: Genevieve
authors.initials: G
authors.lastname: Evin
authors.forename: Qiao-Xin
authors.initials: QX
authors.lastname: Li
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000201:enzymology*; D016229:Amyloid beta-Peptides / Q000097:blood; D000814:Aniline Compounds / Q000097:blood; D015415:Biomarkers; D060825:Cognitive Dysfunction; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D009483:Neuropsychological Tests; D013844:Thiazoles / Q000097:blood
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D015415:Biomarkers; D013844:Thiazoles; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9