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）可将神经毒性血浆来源的成分，细胞和病原体拒之门外。在痴呆症，神经退行性疾病和/或脑萎缩发生之前，阿尔茨海默氏病（AD）中已显示出早期的BBB分解和/或功能障碍。然而，BBB分解在神经退行性疾病中的作用仍不完全清楚。在这里，我们在经常用于研究AD病理生理的动物模型中检查了BBB的分解，包括表达人淀粉样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（AD的最强遗传危险因子）。我们讨论了BBB分解和功能异常在神经退行性过程中的作用，BBB测量中的陷阱以及针对BBB的作用如何影响神经系统疾病的病程。最后，