Journal Article (Review Article)

DZNE-2024-00619

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Is CAA a perivascular brain clearance disease? A discussion of the evidence to date and outlook for future studies.

van Veluw, S. J. ; Benveniste, H. ; Bakker, E. N. T. P. ; Carare, R. O. ; Greenberg, S. M. ; Iliff, J. J. ; Lorthois, S. ; Van Nostrand, W. E. ; Petzold, G. C.DZNE* ; Shih, A. Y. ; van Osch, M. J. P.

2024
Springer International Publishing AG Cham (ZG)

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Please use a persistent id in citations: doi:10.1007/s00018-024-05277-1

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.

Keyword(s): Humans (MeSH) ; Brain: metabolism (MeSH) ; Brain: pathology (MeSH) ; Cerebral Amyloid Angiopathy: metabolism (MeSH) ; Cerebral Amyloid Angiopathy: pathology (MeSH) ; Animals (MeSH) ; Amyloid beta-Peptides: metabolism (MeSH) ; Glymphatic System: metabolism (MeSH) ; Glymphatic System: pathology (MeSH) ; Alzheimer Disease: metabolism (MeSH) ; Alzheimer Disease: pathology (MeSH) ; Brain clearance ; Cerebral amyloid angiopathy ; Cerebrospinal fluid ; Glymphatics ; IPAD ; Perivascular spaces ; Amyloid beta-Peptides

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Contributing Institute(s):

1. Vascular Neurology (AG Petzold ; AG Petzold)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2024

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Database coverage:
; ; ; BIOSIS Previews ; BIOSIS Reviews Reports And Meetings ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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