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Updated: Jun 22, 2026

In Vitro Assays to Assess Blood-brain Barrier Mesh-like Vessel Formation and Disruption
Published on: June 20, 2017
Vascular endothelial barrier dysfunction mediated by amyloid-beta proteins.
Enika Nagababu1, Peter V Usatyuk, Divya Enika
1Molecular Dynamics Section, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Alzheimer's disease (AD) involves neuronal inflammation. Amyloid-beta (A beta) fibrils increase blood vessel permeability by altering cell structure, not via hydrogen peroxide, contributing to AD pathogenesis.
Area of Science:
- Neuroscience
- Cell Biology
- Pathology
Background:
- Neuronal inflammation is a hallmark of Alzheimer's disease (AD).
- Neutrophil infiltration across the blood-brain barrier, facilitated by increased endothelial permeability, contributes to AD pathogenesis.
- Amyloid-beta (A beta) fibril deposition in vasculature and neurons is implicated in AD development.
Purpose of the Study:
- To investigate the effect of A beta fibrils on endothelial permeability.
- To elucidate the underlying mechanisms responsible for A beta-induced permeability changes.
Main Methods:
- Utilized bovine pulmonary arterial endothelial cells.
- Measured transendothelial electrical resistance to assess permeability.
- Analyzed changes in cytosolic Ca+2, tyrosine phosphorylation, and actin cytoskeleton.
Main Results:
- A beta(1-40) and A beta(1-42) fibrils, but not monomers, dose- and time-dependently increased endothelial permeability.
- Catalase partially inhibited the permeability increase (25%), suggesting hydrogen peroxide is not the primary mediator.
- A beta fibrils induced actin stress fiber formation, disruption, aggregation, and cellular gap formation.
Conclusions:
- A beta fibrils increase endothelial permeability through mechanisms independent of significant hydrogen peroxide production.
- The primary mechanism involves alterations to the endothelial cell cytoskeleton, leading to gap formation and increased permeability.
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