Blood platelets in the progression of Alzheimer's disease.
Blood platelets in the progression of Alzheimer's disease.
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DOI：
10.1371/journal.pone.0090523
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Elvers M
中科院分区：
文献类型：
--
作者：
Gowert NS;Donner L;Chatterjee M;Eisele YS;Towhid ST;Münzer P;Walker B;Ogorek I;Borst O;Grandoch M;Schaller M;Fischer JW;Gawaz M;Weggen S;Lang F;Jucker M;Elvers M
阿尔茨海默病（Alzheimer's disease，AD）是一种以脑血管和脑实质中神经毒性淀粉样蛋白斑块形成为特征的疾病，称为脑淀粉样血管病（cerebral amyloid angiopathy，CAA）。除CAA外，AD与血管疾病如中风和动脉粥样硬化密切相关。AD患者发生脑血管功能障碍，导致血流改变，这可能在AD病理学中起重要作用，伴有神经元丢失和记忆缺陷。血小板是止血和血栓形成的主要参与者，但也参与神经炎性疾病如AD。由于血小板具有产生淀粉样蛋白（amyloid-β，AAPs）的活性，因此，血小板作为研究AD病理生理学的外周模型已被广泛接受。此外，血小板被认为是AD早期诊断的生物标志物。然而，腺苷三磷酸肽对血小板的作用以及血小板在AD进展中的影响仍然不明确。本研究探讨了血小板中A β触发的细胞机制。用Ablad 3处理血小板导致血小板活化和活性氧（ROS）和膜混乱的产生增强，表明血小板凋亡增强。更重要的是，血小板将可溶性血小板调节成纤维状结构，这些纤维状结构被凋亡的血小板吸收，但不被活的血小板吸收。这与体外和体内流动下增强的血小板粘附以及AD转基因小鼠脑血管淀粉样蛋白沉积处的血小板积聚一起表明，血小板是CAA诱导血管淀粉样蛋白斑块处血小板血栓形成的主要贡献者，导致对脑血管事件如中风至关重要的血管闭塞。
Alzheimer’s disease (AD) is characterized by neurotoxic amyloid-ß plaque formation in brain parenchyma and cerebral blood vessels known as cerebral amyloid angiopathy (CAA). Besides CAA, AD is strongly related to vascular diseases such as stroke and atherosclerosis. Cerebrovascular dysfunction occurs in AD patients leading to alterations in blood flow that might play an important role in AD pathology with neuronal loss and memory deficits. Platelets are the major players in hemostasis and thrombosis, but are also involved in neuroinflammatory diseases like AD. For many years, platelets were accepted as peripheral model to study the pathophysiology of AD because platelets display the enzymatic activities to generate amyloid-ß (Aß) peptides. In addition, platelets are considered to be a biomarker for early diagnosis of AD. Effects of Aß peptides on platelets and the impact of platelets in the progression of AD remained, however, ill-defined. The present study explored the cellular mechanisms triggered by Aß in platelets. Treatment of platelets with Aß led to platelet activation and enhanced generation of reactive oxygen species (ROS) and membrane scrambling, suggesting enhanced platelet apoptosis. More important, platelets modulate soluble Aß into fibrillar structures that were absorbed by apoptotic but not vital platelets. This together with enhanced platelet adhesion under flow ex vivo and in vivo and platelet accumulation at amyloid deposits of cerebral vessels of AD transgenic mice suggested that platelets are major contributors of CAA inducing platelet thrombus formation at vascular amyloid plaques leading to vessel occlusion critical for cerebrovascular events like stroke.
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DOI：
10.1523/jneurosci.3088-11.2011
发表时间：
2011-10-12
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Langer F;Eisele YS;Fritschi SK;Staufenbiel M;Walker LC;Jucker M
通讯作者：
Jucker M
影响因子：
10.4
作者：
Elvers, M.;Pozgaj, R.;Nieswandt, B.
通讯作者：
Nieswandt, B.
缺乏磷脂酶D1的小鼠中的α（IIB）β（3）整联蛋白活化和剪切依赖性血栓形成。
影响因子：
7.3
作者：
Elvers M;Stegner D;Hagedorn I;Kleinschnitz C;Braun A;Kuijpers ME;Boesl M;Chen Q;Heemskerk JW;Stoll G;Frohman MA;Nieswandt B
通讯作者：
Nieswandt B
影响因子：
64.8
作者：
KITAGUCHI, N;TAKAHASHI, Y;ITO, H
通讯作者：
ITO, H
影响因子：
10.4
作者：
Leytin, V.;Allen, D. J.;Freedman, J.
通讯作者：
Freedman, J.