PDF(Pubmed)
Abstract：
The brain\'s network of perivascular channels for clearance of excess fluids and waste plays a critical role in the pathogenesis of several neurodegenerative diseases including cerebral amyloid angiopathy (CAA). CAA is the main cause of hemorrhagic stroke in the elderly, the most common vascular comorbidity in Alzheimer\'s disease and also implicated in adverse events related to anti-amyloid immunotherapy. Remarkably, the mechanisms governing perivascular clearance of soluble amyloid β-a key culprit in CAA-from the brain to draining lymphatics and systemic circulation remains poorly understood. This knowledge gap is critically important to bridge for understanding the pathophysiology of CAA and accelerate development of targeted therapeutics. The authors of this review recently converged their diverse expertise in the field of perivascular physiology to specifically address this problem within the framework of a Leducq Foundation Transatlantic Network of Excellence on Brain Clearance. This review discusses the overarching goal of the consortium and explores the evidence supporting or refuting the role of impaired perivascular clearance in the pathophysiology of CAA with a focus on translating observations from rodents to humans. We also discuss the anatomical features of perivascular channels as well as the biophysical characteristics of fluid and solute transport.
摘要：
用于清除多余液体和废物的血管周围通道的大脑网络在包括脑淀粉样血管病（CAA）在内的几种神经退行性疾病的发病机理中起着至关重要的作用。CAA是老年人出血性中风的主要病因,阿尔茨海默病最常见的血管合并症，也与抗淀粉样蛋白免疫治疗相关的不良事件有关。值得注意的是,对血管周清除可溶性淀粉样蛋白β的机制-从大脑到引流淋巴管和全身循环的CAA的关键罪魁祸首仍然知之甚少。这种知识差距对于理解CAA的病理生理学和加速靶向治疗的发展至关重要。这篇综述的作者最近融合了他们在血管周生理学领域的各种专业知识，在Leducq基金会跨大西洋卓越脑清除网络的框架内专门解决了这个问题。这篇综述讨论了该联盟的总体目标，并探讨了支持或驳斥血管周清除受损在CAA病理生理学中的作用的证据，重点是将观察结果从啮齿动物转化为人类。我们还讨论了血管周围通道的解剖特征以及流体和溶质运输的生物物理特征。
