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Article Dans Une Revue Cellular and Molecular Life Sciences Année : 2024

Is CAA a perivascular brain clearance disease? A discussion of the evidence to date and outlook for future studies

Susanne J van Veluw
Helene Benveniste
  • Fonction : Auteur
Erik N T P Bakker
  • Fonction : Auteur
Roxana O Carare
  • Fonction : Auteur
Steven M Greenberg
  • Fonction : Auteur
Jeffrey J Iliff
  • Fonction : Auteur
William E van Nostrand
  • Fonction : Auteur
Gabor C Petzold
  • Fonction : Auteur
Andy Y Shih
  • Fonction : Auteur
Matthias J P van Osch
  • Fonction : Auteur

Résumé

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.
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Dates et versions

hal-04593348 , version 1 (29-05-2024)

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Susanne J van Veluw, Helene Benveniste, Erik N T P Bakker, Roxana O Carare, Steven M Greenberg, et al.. Is CAA a perivascular brain clearance disease? A discussion of the evidence to date and outlook for future studies. Cellular and Molecular Life Sciences, 2024, 81 (1), pp.239. ⟨10.1007/s00018-024-05277-1⟩. ⟨hal-04593348⟩
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