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Clearance of interstitial fluid (ISF) and CSF (CLIC) group-part of Vascular Professional Interest Area (PIA): Cerebrovascular disease and the failure of elimination of Amyloid-β from the brain and retina with age and Alzheimer's disease-Opportunities for Therapy
Alzheimers Dement (Amst). 2020 Aug 3;12(1):e12053. doi: 10.1002/dad2.12053.
Roxana O Carare 1, Roxana Aldea 2, Nivedita Agarwal 3, Brian J Bacskai 4, Ingo Bechman 5, Delphine Boche 1, Guojun Bu 6, Diederik Bulters 1 7, Alt Clemens 4, Scott E Counts 8, Mony de Leon 9, Per K Eide 10, Silvia Fossati 11, Steven M Greenberg 4, Edith Hamel 12, Cheryl A Hawkes 13, Maya Koronyo-Hamaoui 14, Atticus H Hainsworth 15, David Holtzman 16, Masafumi Ihara 17, Angela Jefferson 18, Raj N Kalaria 19, Christopher M Kipps 1 7, Katja M Kanninen 20, Ville Leinonen 20, JoAnne McLaurin 21, Scott Miners 22, Tarja Malm 20, James A R Nicoll 1 6, Fabrizio Piazza 23, Gesine Paul 24, Steven M Rich 25, Satoshi Saito 17, Andy Shih 26, Henrieta Scholtzova 27, Heather Snyder 28, Peter Snyder 29, Finnbogi Rutur Thormodsson 30, Susanne J van Veluw 4, Roy O Weller 1, David J Werring 31, Donna Wilcock 32, Mark R Wilson 33, Berislav V Zlokovic 34, Ajay Verma 35
Abstract:
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.
PMID: 32775596
Free Full-Text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396859/