Alzheimer's Disease Severity Is Associated with an Imbalance in Serum Levels of Enzymes Regulating Plasmin Synthesis.
Alzheimer's Disease Severity Is Associated with an Imbalance in Serum Levels of Enzymes Regulating Plasmin Synthesis.
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DOI：
10.3390/ph15091074
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发表时间：
2022-08-29
期刊：
影响因子：
--
通讯作者：
Hort J
中科院分区：
文献类型：
--
作者：
Angelucci F;Veverova K;Katonová A;Piendel L;Vyhnalek M;Hort J
阿尔茨海默病（AD）是一种中枢神经系统（CNS）疾病，其特征在于记忆、认知功能丧失和神经变性。纤溶酶是一种降解许多血浆蛋白的酶。在CNS中，纤溶酶可减少β淀粉样蛋白（Aβ）的蓄积，并具有与AD病理生理学相关的其他作用。脑纤溶酶的合成受两种酶的调节：一种是激活性的组织纤溶酶原激活物（tPA），另一种是抑制性的纤溶酶原激活物抑制剂-1（派-1）。我们调查了40名AD和40名遗忘型轻度认知功能障碍（aMCI）患者血清中tPA和派-1的水平，并与10名认知健康对照组进行了比较。此外，我们还检查了这些患者组中的派-1/tPA比值。收集静脉血，并使用夹心ELISA定量派-1和tPA血清浓度。结果表明，AD和aMCI患者血浆派-1水平升高。这种增加与使用简易精神状态检查（MMSE）测量的认知表现呈负相关。类似地，tPA和派-1之间的比率在aMCI和AD患者中逐渐增加。这项研究表明，AD和aMCI患者具有改变的派-1血清水平和派-1/tPA比率。由于这些酶是纤溶酶的CNS调节剂，派-1血清水平可能是反映AD认知功能下降的标志物。
Alzheimer’s disease (AD) is a central nervous system (CNS) disease characterized by loss of memory, cognitive functions, and neurodegeneration. Plasmin is an enzyme degrading many plasma proteins. In the CNS, plasmin may reduce the accumulation of beta amyloid (Aβ) and have other actions relevant to AD pathophysiology. Brain plasmin synthesis is regulated by two enzymes: one activating, the tissue plasminogen activator (tPA), and the other inhibiting, the plasminogen activator inhibitor-1 (PAI-1). We investigated the levels of tPA and PAI-1 in serum from 40 AD and 40 amnestic mild cognitively impaired (aMCI) patients compared to 10 cognitively healthy controls. Moreover, we also examined the PAI-1/tPA ratio in these patient groups. Venous blood was collected and the PAI-1 and tPA serum concentrations were quantified using sandwich ELISAs. The results showed that PAI-1 levels increased in AD and aMCI patients. This increase negatively correlated with cognitive performance measured using the Mini-Mental Status Exam (MMSE). Similarly, the ratio between tPA and PAI-1 gradually increases in aMCI and AD patients. This study demonstrates that AD and aMCI patients have altered PAI-1 serum levels and PAI-1/tPA ratio. Since these enzymes are CNS regulators of plasmin, PAI-1 serum levels could be a marker reflecting cognitive decline in AD.
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DOI：
10.1016/j.jalz.2011.03.005
发表时间：
2011-05
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
McKhann GM;Knopman DS;Chertkow H;Hyman BT;Jack CR Jr;Kawas CH;Klunk WE;Koroshetz WJ;Manly JJ;Mayeux R;Mohs RC;Morris JC;Rossor MN;Scheltens P;Carrillo MC;Thies B;Weintraub S;Phelps CH
通讯作者：
Phelps CH
影响因子：
5.6
作者：
Miszta A;Huskens D;Donkervoort D;Roberts MJM;Wolberg AS;de Laat B
通讯作者：
de Laat B
DOI：
10.1111/j.1582-4934.2011.01394.x
发表时间：
2012-04-01
影响因子：
5.3
作者：
Barker, Rachel;Kehoe, Patrick G.;Love, Seth
通讯作者：
Love, Seth
影响因子：
4.2
作者：
Liu, R-M;van Groen, T.;Katre, A.;Cao, D.;Kadisha, I.;Ballinger, C.;Wang, L.;Carroll, S. L.;Li, L.
通讯作者：
Li, L.
影响因子：
6.1
作者：
Marsh J;Alifragis P
通讯作者：
Alifragis P