Alterations of matrix metalloproteinases in the healthy elderly with increased risk of prodromal Alzheimer's disease.
Alterations of matrix metalloproteinases in the healthy elderly with increased risk of prodromal Alzheimer's disease.
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DOI：
10.1186/alzrt44
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发表时间：
2010-06-24
期刊：
影响因子：
--
通讯作者：
Hansson O
中科院分区：
文献类型：
--
作者：
Stomrud E;Björkqvist M;Janciauskiene S;Minthon L;Hansson O
基质金属蛋白酶（MMP）被认为参与了阿尔茨海默病（AD）的病理过程。在这项研究中，我们的目的是检查脑脊液（CSF）中的基质金属蛋白酶和金属蛋白酶组织抑制剂-1（TIMP-1）的水平在个人与AD痴呆和认知健康的老年人，并探讨其与建立阿尔茨海默病的CSF生物标志物的关系。收集了38名AD痴呆患者和34名认知健康的老年人的CSF。分析CSF中MMP-1、MMP-3、MMP-9、TIMP-1、β-淀粉样蛋白1 -42（Aβ42）、总tau蛋白（T-tau）和磷酸化tau蛋白（P-tau）。计算MMP/TIMP-1比值。确定参与者的APOE基因型。与认知健康个体相比，AD患者具有较高的MMP-9/TIMP-1比值和较低的TIMP-1水平。在AD患者中，MMP-9/TIMP-1比值与CSF T-tau（神经变性的标志物）相关。有趣的是，与无风险标志物的健康个体相比，具有未来AD风险标志物（即AD支持性CSF生物标志物T-tau、P-tau和Aβ42水平或存在APOE ε4等位基因）的认知健康个体具有更高的CSF MMP-3和MMP-9水平以及更高的CSF MMP-3/TIMP-1比值。对照组CSF中MMP-3和MMP-9的水平也与CSF中T-tau和P-tau水平相关。这项研究表明，MMP-3和MMP-9可能参与AD的早期发病机制，MMP可能与神经元变性和神经元缠结的形成相关，甚至在发展明显的认知功能障碍之前。
Matrix metalloproteinases (MMP) are believed to be involved in the pathologic processes behind Alzheimer's disease (AD). In this study, we aimed to examine the cerebrospinal fluid (CSF) levels of MMPs and tissue inhibitors of metalloproteinase-1 (TIMP-1) in individuals with AD dementia and cognitively healthy elderly individuals, and to investigate their relationship with established CSF biomarkers for Alzheimer's disease. CSF was collected from 38 individuals with AD dementia and 34 cognitively healthy elderly individuals. The CSF was analyzed for MMP-1, MMP-3, MMP-9, TIMP-1, β-amyloid1-42 (Aβ42), total tau protein (T-tau) and phosphorylated tau protein (P-tau). MMP/TIMP-1 ratios were calculated. APOE genotype was determined for the participants. AD patients had higher MMP-9/TIMP-1 ratios and lower TIMP-1 levels compared to cognitively healthy individuals. In AD patients, the MMP-9/TIMP-1 ratio correlated with CSF T-tau, a marker of neurodegeneration. Interestingly, the cognitively healthy individuals with risk markers for future AD, i.e. AD-supportive CSF biomarker levels of T-tau, P-tau and Aβ42 or the presence of the APOE ε4 allele, had higher CSF MMP-3 and MMP-9 levels and higher CSF MMP-3/TIMP-1 ratios compared to the healthy individuals without risk markers. The CSF levels of MMP-3 and -9 in the control group also correlated with the CSF T-tau and P-tau levels. This study indicates that MMP-3 and MMP-9 might be involved in early pathogenesis of AD and that MMPs could be associated with neuronal degeneration and formation of neurofibrillary tangles even prior to development of overt cognitive dysfunction.
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DOI：
10.1016/s0140-6736(20)32205-4
发表时间：
2021-04-24
期刊：
Lancet (London, England)
影响因子：
--
作者：
Scheltens P;De Strooper B;Kivipelto M;Holstege H;Chételat G;Teunissen CE;Cummings J;van der Flier WM
通讯作者：
van der Flier WM
影响因子：
4.2
作者：
Helbecque, Nicole;Cottel, Dominique;Amouyel, Philippe
通讯作者：
Amouyel, Philippe
影响因子：
3.4
作者：
Jourquin, J;Tremblay, EN;Rivera, S
通讯作者：
Rivera, S
影响因子：
11
作者：
Gustafson, Deborah R.;Skoog, Ingmar;Blennow, Kaj
通讯作者：
Blennow, Kaj
影响因子：
9.9
作者：
Li, G.;Sokal, I.;Montine, T. J.
通讯作者：
Montine, T. J.