Vascular endothelial barrier dysfunction mediated by amyloid-β proteins

Enika Nagababu, Peter V. Usatyuk, Divya Enika, Viswanathan Natarajan, Joseph M. Rifkind

Research output: Contribution to journalArticle

Abstract

Neuronal inflammation is very common in Alzheimer's disease (AD). This inflammation can be caused by infiltration of neutrophils across the blood brain barrier. Endothelial permeability changes are required for the infiltration of high molecular weight components to the brain. Deposition of toxic amyloid-β (Aβ) fibrils in the cerebral vasculature, as well as in brain neurons, has been implicated in the development of AD. This study investigates the effect of Aβ fibrils on the permeability of the endothelium and the mechanism for the observed permeability changes. Aβ-{1-40} and Aβ-{1-42} fibrils, but not monomers, were found to increase permeability of bovine pulmonary arterial endothelial cells in a dose- and time dependent manner as detected by transendothelial electrical resistance. This increase in permeability is only partially (25%) inhibited by catalase and is not associated with an increase in cytosolic Ca^{+2} or tyrosine phosphorylation. These results indicate that hydrogen peroxide is not the primary mediator for the permeability changes. Treatment of cells with both amyloid fibrils resulted in stress fiber formation, disruption and aggregation of actin filaments, and cellular gap formation. The results of this study reveal that Aβ increases the permeability of endothelium by inducing change in the cytoskeleton network.

Original languageEnglish (US)
Pages (from-to)845-854
Number of pages10
JournalJournal of Alzheimer's Disease
Volume17
Issue number4
DOIs
StatePublished - 2009

Keywords

  • Alzheimer's disease
  • Amyloid-β
  • Endothelial cells
  • Permeability

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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  • Cite this

    Nagababu, E., Usatyuk, P. V., Enika, D., Natarajan, V., & Rifkind, J. M. (2009). Vascular endothelial barrier dysfunction mediated by amyloid-β proteins. Journal of Alzheimer's Disease, 17(4), 845-854. https://doi.org/10.3233/JAD-2009-1104