Blood-Brain Barrier Dysfunction in Normal Aging and Neurodegeneration: Mechanisms, Impact, and Treatments

Cerebral endothelial cells and their linking tight junctions form a unique, dynamic and multi-functional interface, the blood-brain barrier (BBB). The endothelium is regulated by perivascular cells and components forming the neurovascular unit. This review examines BBB and neurovascular unit changes...

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Bibliographic Details
Published in:Stroke (1970) 2023-03, Vol.54 (3), p.661-672
Main Authors: Andjelkovic, Anuska V., Situ, Muyu, Citalan-Madrid, Ali Francisco, Stamatovic, Svetlana M., Xiang, Jianming, Keep, Richard F.
Format: Article
Language:English
Subjects:
Aging
Alzheimer Disease
Blood-Brain Barrier
Cerebral Amyloid Angiopathy
Endothelial Cells
Humans
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Summary:Cerebral endothelial cells and their linking tight junctions form a unique, dynamic and multi-functional interface, the blood-brain barrier (BBB). The endothelium is regulated by perivascular cells and components forming the neurovascular unit. This review examines BBB and neurovascular unit changes in normal aging and in neurodegenerative disorders, particularly focusing on Alzheimer disease, cerebral amyloid angiopathy and vascular dementia. Increasing evidence indicates BBB dysfunction contributes to neurodegeneration. Mechanisms underlying BBB dysfunction are outlined (endothelium and neurovascular unit mediated) as is the BBB as a therapeutic target including increasing the uptake of systemically delivered therapeutics across the BBB, enhancing clearance of potential neurotoxic compounds via the BBB, and preventing BBB dysfunction. Finally, a need for novel biomarkers of BBB dysfunction is addressed.
ISSN:0039-2499
1524-4628
DOI:10.1161/STROKEAHA.122.040578