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Mol. Life Sci."],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The brain\u2019s 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\u2019s disease and also implicated in adverse events related to anti-amyloid immunotherapy. Remarkably, the mechanisms governing perivascular clearance of soluble amyloid \u03b2\u2014a key culprit in CAA\u2014from 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.<\/jats:p>","DOI":"10.1007\/s00018-024-05277-1","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T00:01:27Z","timestamp":1716768087000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Is CAA a perivascular brain clearance disease? 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Author S.G. has served as a consultant for Eli Lily, as a safety monitoring committee member for Bayer and IQVIA\/Washington University, and as a scientific advisory board member for MIAC, and has received industry support in the form of a sponsored research agreement from Alnylam. Author J.I. serves as the Chair for the Scientific Advisory Board of Applied Cognition, Inc. He received compensation for this work and holds an equity stake in this company. Author M.v.O has received industry support from Philips and serves as a consultant for Alnylam. Author W.V.N. has received industry support from Alnylam. Author S.v.V. has received industry support in the form of a sponsored research agreement from Therini Bio and Sanofi and has served as a consultant for Biogen and Eisai.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"N\/a.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"N\/a.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}],"article-number":"239"}}