Montagne Axel, Zhao Zhen, Zlokovic Berislav V
Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, Los Angeles, CA.
Department of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, Los Angeles, CA.
J Exp Med. 2017 Nov 6;214(11):3151-3169. doi: 10.1084/jem.20171406. Epub 2017 Oct 23.
The blood-brain barrier (BBB) keeps neurotoxic plasma-derived components, cells, and pathogens out of the brain. An early BBB breakdown and/or dysfunction have been shown in Alzheimer's disease (AD) before dementia, neurodegeneration and/or brain atrophy occur. However, the role of BBB breakdown in neurodegenerative disorders is still not fully understood. Here, we examine BBB breakdown in animal models frequently used to study the pathophysiology of AD, including transgenic mice expressing human amyloid-β precursor protein, presenilin 1, and tau mutations, and apolipoprotein E, the strongest genetic risk factor for AD. We discuss the role of BBB breakdown and dysfunction in neurodegenerative process, pitfalls in BBB measurements, and how targeting the BBB can influence the course of neurological disorder. Finally, we comment on future approaches and models to better define, at the cellular and molecular level, the underlying mechanisms between BBB breakdown and neurodegeneration as a basis for developing new therapies for BBB repair to control neurodegeneration.
血脑屏障（BBB）可阻止神经毒性血浆衍生成分、细胞和病原体进入大脑。在阿尔茨海默病（AD）出现痴呆、神经退行性变和/或脑萎缩之前，就已发现早期血脑屏障破坏和/或功能障碍。然而，血脑屏障破坏在神经退行性疾病中的作用仍未完全明确。在此，我们研究常用于研究AD病理生理学的动物模型中的血脑屏障破坏情况，包括表达人类淀粉样β前体蛋白、早老素1和tau突变的转基因小鼠，以及载脂蛋白E，它是AD最强的遗传风险因素。我们讨论血脑屏障破坏和功能障碍在神经退行性过程中的作用、血脑屏障测量中的陷阱，以及靶向血脑屏障如何影响神经系统疾病的进程。最后，我们对未来的方法和模型进行评论，以便在细胞和分子水平上更好地定义血脑屏障破坏与神经退行性变之间的潜在机制，为开发控制神经退行性变的血脑屏障修复新疗法奠定基础。
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