Investigation of Matrix Metalloproteinases, MMP-2 and MMP-9, in Plasma Reveals a Decrease of MMP-2 in Alzheimer's Disease
Investigation of Matrix Metalloproteinases, MMP-2 and MMP-9, in Plasma Reveals a Decrease of MMP-2 in Alzheimer's Disease
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DOI：
10.3233/jad-2011-101974
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发表时间：
2011-01-01
影响因子：
4
通讯作者：
Li, Qiao-Xin
中科院分区：
文献类型：
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作者：
Lim, Nastasia K-H;Villemagne, Victor L.;Li, Qiao-Xin
阿尔茨海默病（AD）脑中的病理变化包括淀粉样蛋白-β（A β）斑块和神经元缠结，以及神经元死亡和突触丧失。已知基质金属蛋白酶MMP-2和MMP-9降解A β，并且它们的表达在AD脑中增加，特别是在淀粉样斑块周围的星形胶质细胞中。为了研究血浆金属蛋白酶与AD之间的可能关联，我们定量了健康对照（HC，n = 56）、轻度认知障碍（MCI，n = 48）和AD（n = 50）患者血浆中MMP-2和MMP-9的活性。所有病例之前均接受过匹兹堡化合物B（PiB）成像，并进行了简易精神状态检查（MMSE）评估。明胶酶谱法测定MMP-2和MMP-9活性。与HC相比，AD组MMP-2活性显著降低1.5倍（p < 0.001），与MCI相比降低1.4倍（p < 0.01）。三组间MMP-9水平无差异。MMP-2血浆活性与MMSE评分呈正相关（r = 0.16，p < 0.05），与PiB无相关性。这是第一次报告的MMP-2活性在AD血浆中的变化，这些研究结果可能提供一些洞察AD的发病机制。
Pathological changes in the Alzheimer's disease (AD) brain include amyoid-beta (A beta) plaques, and neurofibrillary tangles, as well as neuronal death and synaptic loss. Matrix metalloproteinases MMP-2 and MMP-9 are known to degrade A beta, 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 = 48), 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.