TY  - JOUR
AU  - van Veluw, Susanne J
AU  - Benveniste, Helene
AU  - Bakker, Erik N T P
AU  - Carare, Roxana O
AU  - Greenberg, Steven M
AU  - Iliff, Jeffrey J
AU  - Lorthois, Sylvie
AU  - Van Nostrand, William E
AU  - Petzold, Gabor C
AU  - Shih, Andy Y
AU  - van Osch, Matthias J P
TI  - Is CAA a perivascular brain clearance disease? A discussion of the evidence to date and outlook for future studies.
JO  - Cellular and molecular life sciences
VL  - 81
IS  - 1
SN  - 1420-682X
CY  - Cham (ZG)
PB  - Springer International Publishing AG
M1  - DZNE-2024-00619
SP  - 239
PY  - 2024
AB  - 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.
KW  - Humans
KW  - Brain: metabolism
KW  - Brain: pathology
KW  - Cerebral Amyloid Angiopathy: metabolism
KW  - Cerebral Amyloid Angiopathy: pathology
KW  - Animals
KW  - Amyloid beta-Peptides: metabolism
KW  - Glymphatic System: metabolism
KW  - Glymphatic System: pathology
KW  - Alzheimer Disease: metabolism
KW  - Alzheimer Disease: pathology
KW  - Brain clearance (Other)
KW  - Cerebral amyloid angiopathy (Other)
KW  - Cerebrospinal fluid (Other)
KW  - Glymphatics (Other)
KW  - IPAD (Other)
KW  - Perivascular spaces (Other)
KW  - Amyloid beta-Peptides (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC11130115
C6  - pmid:38801464
DO  - DOI:10.1007/s00018-024-05277-1
UR  - https://pub.dzne.de/record/269784
ER  -