Fibrin deposited in the Alzheimer's disease brain promotes neuronal degeneration.
Fibrin deposited in the Alzheimer's disease brain promotes neuronal degeneration.
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DOI：
10.1016/j.neurobiolaging.2014.10.030
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发表时间：
2015-02
影响因子：
4.2
通讯作者：
Strickland S
中科院分区：
文献类型：
--
作者：
Cortes-Canteli M;Mattei L;Richards AT;Norris EH;Strickland S
阿尔茨海默病(AD)是痴呆症最常见的形式，没有有效的治疗方法。除了众所周知的病理特征，这种疾病也有血管成分，大量证据表明血栓增加以及纤维蛋白(原)在AD中的关键作用。这种分子与阿尔茨海默病中观察到的神经炎症、神经血管损伤、血脑屏障通透性、血管淀粉样蛋白沉积和记忆缺陷有关。在这里，我们提出的证据表明，纤维蛋白沉积增加，在AD的大脑，并与病理程度相关。此外，我们发现纤维蛋白(原)存在于营养不良的神经突起区域，纤维蛋白原水平的适度下降改善了AD小鼠下丘脑神经元的健康状况，并改善了淀粉样蛋白的病理。我们的结果进一步说明了纤维蛋白(原)在这种疾病中的重要作用，并支持了旨在阻断纤维蛋白原和Aβ之间的相互作用和/或使AD中增加的血栓正常化的治疗策略的设计。
Alzheimer’s disease (AD) is the most common form of dementia and has no effective treatment. Besides the well-known pathological characteristics, this disease also has a vascular component, and substantial evidence shows increased thrombosis as well as a critical role for fibrin(ogen) in AD. This molecule has been implicated in neuroinflammation, neurovascular damage, blood brain barrier permeability, vascular amyloid deposition, and memory deficits that are observed in AD. Here we present evidence demonstrating that fibrin deposition increases in the AD brain and correlates with the degree of pathology. Moreover, we show that fibrin(ogen) is present in areas of dystrophic neurites and that a modest decrease in fibrinogen levels improves neuronal health and ameliorates amyloid pathology in the subiculum of AD mice. Our results further characterize the important role of fibrin(ogen) in this disease and support the design of therapeutic strategies aimed at blocking the interaction between fibrinogen and Aβ and/or normalizing the increased thrombosis present in AD.
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影响因子：
12.7
作者：
Iadecola C
通讯作者：
Iadecola C
影响因子：
16.2
作者：
Cortes-Canteli, Marta;Paul, Justin;Norris, Erin H.;Bronstein, Robert;Ahn, Hyung Jin;Zamolodchikov, Daria;Bhuvanendran, Shivaprasad;Fenz, Katherine M.;Strickland, Sidney
通讯作者：
Strickland, Sidney
影响因子：
14
作者：
Brookmeyer, Ron;Johnson, Elizabeth;Arrighi, H. Michael
通讯作者：
Arrighi, H. Michael
DOI：
10.1046/j.1365-2362.2002.00994.x
发表时间：
2002-05-01
影响因子：
5.5
作者：
Fiala, M;Liu, QN;Vinters, HV
通讯作者：
Vinters, HV
影响因子：
12.7
作者：
Duyckaerts C;Potier MC;Delatour B
通讯作者：
Delatour B