Discerning the Role of Blood Brain Barrier Dysfunction in Alzheimer's Disease.
Discerning the Role of Blood Brain Barrier Dysfunction in Alzheimer's Disease.
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DOI：
10.14336/ad.2022.0130-1
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发表时间：
2022-10-01
影响因子：
7.4
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中科院分区：
文献类型：
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阿尔茨海默病（AD）是最常见的神经退行性疾病。AD的主要特征是淀粉样蛋白-β（Aβ）和过度磷酸化的tau在脑中的积累。血脑屏障（Blood brain barrier，BBB）功能障碍是认知功能障碍的重要原因之一。然而，BBB功能障碍在AD发病机制中的作用仍不完全清楚。BBB功能障碍是否是Aβ病理学、tau病理学、神经炎症或其他病症的结果或致病事实仍然是难以捉摸的。本文综述了AD患者血脑屏障功能障碍的主要发现，以及血脑屏障功能障碍与Aβ病理、tau蛋白病理和神经炎症之间的相互关系。此外，提出了AD中BBB功能障碍对递送治疗药物的影响。最后，我们讨论了如何更好地确定BBB功能障碍和AD之间的潜在机制，以及如何探索新的BBB调节治疗AD的未来。
Alzheimer’s disease (AD) is the most common form of neurodegenerative disease. The predominant characteristics of AD are the accumulation of amyloid-β (Aβ) and hyperphosphorylated tau in the brain. Blood brain barrier (BBB) dysfunction as one of the causative factors of cognitive impairment is increasingly recognized in the last decades. However, the role of BBB dysfunction in AD pathogenesis is still not fully understood. It remains elusive whether BBB dysfunction is a consequence or causative fact of Aβ pathology, tau pathology, neuroinflammation, or other conditions. In this review, we summarized the major findings of BBB dysfunction in AD and the reciprocal relationships between BBB dysfunction, Aβ pathology, tau pathology, and neuroinflammation. In addition, the implications of BBB dysfunction in AD for delivering therapeutic drugs were presented. Finally, we discussed how to better determine the underlying mechanisms between BBB dysfunction and AD, as well as how to explore new therapies for BBB regulation to treat AD in the future.