Affiliations: [a] Department of Pathology, The University of Melbourne, Parkville Vic, Australia | [b] Department of Nuclear Medicine, Austin Health, Vic, Australia | [c] Mental Health Research Institute, The University of Melbourne, Parkville Vic, Australia | [d] Department of Anatomical Pathology, The Alfred Hospital, Commercial Rd, Prahran, Vic., Australia
Correspondence:
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Correspondence to: Qiao-Xin Li, Ph.D, Department of Pathology, The University of Melbourne, Medical Building, level 5, Grattan Street, Parkville Vic 3010, Australia. Tel.: +61 3 8344 5878; Fax: +61 3 8344 4004; E-mail: [email protected].
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.
