Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Department of Anesthesiology, Yale School of Medicine, New Haven, CT, USA.
Cell Mol Life Sci. 2024 May 27;81(1):239. doi: 10.1007/s00018-024-05277-1.
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.
大脑的血管周围通道网络对于清除多余的液体和废物起着至关重要的作用，其与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制有关。CAA 是老年人脑出血的主要原因，也是阿尔茨海默病最常见的血管合并症，并且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，从大脑到引流淋巴管和全身循环的可溶性淀粉样β（CAA 的关键罪魁祸首）的血管周围清除的机制仍知之甚少。为了了解 CAA 的病理生理学并加速靶向治疗的发展，弥合这一知识空白至关重要。本文的作者最近汇集了他们在血管周围生理学领域的不同专业知识，以便在 Leducq 基金会脑清除卓越跨大西洋网络的框架内专门解决这一问题。本文讨论了该联合会的总体目标，并探讨了支持或反驳血管周围清除功能障碍在 CAA 病理生理学中作用的证据，重点是将从啮齿动物到人类的观察结果进行转化。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。
