The amyloid-β protein (Aβ) protein plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). It is believed that Aβ deposited in the brain originates from the brain tissue itself. However, Aβ is generated in both brain and peripheral tissues. Whether circulating Aβ contributes to brain AD-type pathologies remains largely unknown. In this study, using a model of parabiosis between APPswe/PS1dE9 transgenic AD mice and their wild-type littermates, we observed that the human Aβ originated from transgenic AD model mice entered the circulation and accumulated in the brains of wild-type mice, and formed cerebral amyloid angiopathy and Aβ plaques after a 12-month period of parabiosis. AD-type pathologies related to the Aβ accumulation including tau hyperphosphorylation, neurodegeneration, neuroinflammation and microhemorrhage were found in the brains of the parabiotic wild-type mice. More importantly, hippocampal CA1 long-term potentiation was markedly impaired in parabiotic wild-type mice. To the best of our knowledge, our study is the first to reveal that blood-derived Aβ can enter the brain, form the Aβ-related pathologies and induce functional deficits of neurons. Our study provides novel insight into AD pathogenesis and provides evidence that supports the development of therapies for AD by targeting Aβ metabolism in both the brain and the periphery.

中文翻译：

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血液来源的淀粉样β蛋白可诱发阿尔茨海默氏病。

淀粉样β蛋白（Aβ）蛋白在阿尔茨海默氏病（AD）的发病机理中起关键作用。认为沉积在脑中的Aβ源自脑组织本身。然而，Aβ在脑和外周组织中均产生。循环中的Aβ是否有助于脑AD型病理仍是未知之数。在这项研究中，使用APPswe / PS1dE9转基因AD小鼠与其野生型同窝小鼠之间的共生模型，我们观察到源自转基因AD模型小鼠的人Aβ进入循环并在野生型小鼠的大脑中积累，并且在共生12个月后形成脑淀粉样血管病和Aβ斑块。与Aβ积累有关的AD型病理包括tau过度磷酸化，神经退行性变，在副生物野生型小鼠的大脑中发现了神经炎症和微出血。更重要的是，在共生生物野生型小鼠中海马CA1的长期增强作用显着受损。据我们所知，我们的研究是第一个揭示血源性Aβ可以进入大脑，形成与Aβ相关的病理学并诱发神经元功能缺陷的研究。我们的研究为AD发病机制提供了新颖的见解，并提供了通过靶向大脑和周围区域的Aβ代谢来支持AD疗法发展的证据。形成与Aβ有关的病理，并诱导神经元的功能缺陷。我们的研究为AD发病机制提供了新颖的见解，并提供了通过靶向大脑和周围区域的Aβ代谢来支持AD疗法发展的证据。形成与Aβ有关的病理，并诱导神经元的功能缺陷。我们的研究为AD发病机制提供了新颖的见解，并提供了通过靶向大脑和周围区域的Aβ代谢来支持AD疗法发展的证据。