Carare Roxana O, Aldea Roxana, Agarwal Nivedita, Bacskai Brian J, Bechman Ingo, Boche Delphine, Bu Guojun, Bulters Diederik, Clemens Alt, Counts Scott E, de Leon Mony, Eide Per K, Fossati Silvia, Greenberg Steven M, Hamel Edith, Hawkes Cheryl A, Koronyo-Hamaoui Maya, Hainsworth Atticus H, Holtzman David, Ihara Masafumi, Jefferson Angela, Kalaria Raj N, Kipps Christopher M, Kanninen Katja M, Leinonen Ville, McLaurin JoAnne, Miners Scott, Malm Tarja, Nicoll James A R, Piazza Fabrizio, Paul Gesine, Rich Steven M, Saito Satoshi, Shih Andy, Scholtzova Henrieta, Snyder Heather, Snyder Peter, Thormodsson Finnbogi Rutur, van Veluw Susanne J, Weller Roy O, Werring David J, Wilcock Donna, Wilson Mark R, Zlokovic Berislav V, Verma Ajay
University of Southampton Southampton UK.
Roche Innovation Center Basel Basel Switzerland.
Alzheimers Dement (Amst). 2020 Aug 3;12(1):e12053. doi: 10.1002/dad2.12053. eCollection 2020.
Two of the key functions of arteries in the brain are (1) the well-recognized supply of blood via the vascular lumen and (2) the emerging role for the arterial walls as routes for the elimination of interstitial fluid (ISF) and soluble metabolites, such as amyloid beta (Aβ), from the brain and retina. As the brain and retina possess no conventional lymphatic vessels, fluid drainage toward peripheral lymph nodes is mediated via transport along basement membranes in the walls of capillaries and arteries that form the intramural peri-arterial drainage (IPAD) system. IPAD tends to fail as arteries age but the mechanisms underlying the failure are unclear. In some people this is reflected in the accumulation of Aβ plaques in the brain in Alzheimer's disease (AD) and deposition of Aβ within artery walls as cerebral amyloid angiopathy (CAA). Knowledge of the dynamics of IPAD and why it fails with age is essential for establishing diagnostic tests for the early stages of the disease and for devising therapies that promote the clearance of Aβ in the prevention and treatment of AD and CAA. This editorial is intended to introduce the rationale that has led to the establishment of the Clearance of Interstitial Fluid (ISF) and CSF (CLIC) group, within the Vascular Professional Interest Area of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment.
(1)通过血管腔供应血液,这一点已得到广泛认可;(2)动脉壁作为从大脑和视网膜清除间质液(ISF)和可溶性代谢产物(如β淀粉样蛋白(Aβ))的途径,其作用正逐渐显现。由于大脑和视网膜没有传统的淋巴管,朝向外周淋巴结的液体引流是通过沿着形成壁内动脉周围引流(IPAD)系统的毛细血管和动脉壁中的基底膜进行运输来介导的。随着动脉衰老,IPAD往往会失效,但其失效的机制尚不清楚。在一些人身上,这表现为阿尔茨海默病(AD)患者大脑中Aβ斑块的积累以及作为脑淀粉样血管病(CAA)的Aβ在动脉壁内的沉积。了解IPAD的动态变化以及它为何会随着年龄增长而失效,对于建立该疾病早期阶段的诊断测试以及设计促进Aβ清除的疗法以预防和治疗AD及CAA至关重要。这篇社论旨在介绍促使阿尔茨海默病协会国际促进阿尔茨海默病研究与治疗协会血管专业兴趣领域内成立间质液(ISF)和脑脊液清除(CLIC)小组的基本原理。