Concentrations of Matrix Metalloproteinases and their Tissue Inhibitors in the Cerebrospinal Fluid of Patients with Alzheimer's Disease
Concentrations of Matrix Metalloproteinases and their Tissue Inhibitors in the Cerebrospinal Fluid of Patients with Alzheimer's Disease
复制标题
DOI：
10.3233/jad-131634
复制
发表时间：
2014-01-01
影响因子：
4
通讯作者：
Lewczuk, Piotr
中科院分区：
文献类型：
--
作者：
Mroczko, Barbara;Groblewska, Magdalena;Lewczuk, Piotr
背景资料：越来越多的证据表明基质金属蛋白酶（MMPs）及其组织抑制剂（TIMPs）参与神经退行性变过程，但关于其在脑脊液（CSF）中的浓度报道不一致。目的：因此，我们研究的目的是评估CSF中MMP-2、MMP-3、MMP-9、及其抑制剂（TIMP-1和TIMP-2）在仔细选择的阿尔茨海默病（AD）患者组、轻度认知障碍（MCI）患者组和非痴呆对照组中，其临床和神经心理学诊断通过神经化学痴呆诊断的相应CSF生物标志物证实：降低A β（1-42）和/或A β（42/40）比率的浓度，以及增加Tau和pTau 181蛋白的浓度。结果：AD患者脑脊液中MMP-9浓度显著低于对照组，MMP-3浓度显著高于对照组。无论是MMP-2，也没有TIMPs表现出显着的变化之间的组investigated.Conclusion：改变浓度的三个MMP在这项研究中的调查表明，这个家庭的生物分子可能发挥作用，在AD的病理生理。需要进一步的研究来确定其潜在的诊断效用。
Background: A growing body of evidence shows the involvement of matrix metalloproteinases(MMPs) and their tissue inhibitors (TIMPs) in neurodegeneration processes, but reports of their concentrations in the cerebrospinal fluid (CSF) are inconsistent.Objective: Therefore, the aim of our study was to evaluate the CSF concentrations of MMP-2, MMP-3, MMP-9, and their inhibitors (TIMP-1 and TIMP-2) in carefully selected groups of patients with Alzheimer's disease (AD), mild cognitive impairment (MCI), and non-demented controls, whose clinical and neuropsychological diagnoses were confirmed by the corresponding CSF biomarkers of neurochemical dementia diagnostics: decreased concentrations of A beta(1-42) and/or A beta(42/40) ratio, and increased concentrations of Tau and pTau181 proteins.Methods: The study included 33 AD patients, 15 subjects with MCI, and 18 elderly individuals without cognitive deficits. The CSF concentrations of MMPs and TIMPs were determined with ELISAs.Results: CSF concentrations of MMP-9 were significantly lower, and the concentrations of MMP-3 significantly higher in AD patients compared to the controls. Neither MMP-2 nor TIMPs showed significant changes among the groups investigated.Conclusion: Altered concentrations of two out of three MMPs investigated in this study suggest that this family of biomolecules may play a role in the AD pathophysiology. Further studies are needed to establish their potential diagnostic utility.