Abstract
Cerebrovascular dysfunction is a critical component of Alzheimer's disease (AD) pathogenesis. Oligomeric amyloid-β42 (oAβ42) is considered a major contributor to AD progression. However, data are limited on the role of oAβ42 in brain endothelial cell vessel degeneration/angiogenesis, including the interaction with angiogenic mediators. Thus, the current study determined the effect of oAβ42 on angiogenesis in vitro, utilizing single brain endothelial cell cultures and triple cultures mimicking the microvascular unit (MVU: brain endothelial cells, astrocytes, and pericytes). oAβ42 dose-dependently reduced angiogenesis and induced vessel disruption. Critically, epidermal growth factor prevented oAβ42-induced deficits, implicating angiogenic pathways as potential therapeutics for AD.
Keywords:
Alzheimer’s; angiogenesis; blood–brain barrier; cerebrovascular disease; endothelium; pericytes.
© The Author(s) 2016.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alzheimer Disease / metabolism
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Alzheimer Disease / pathology*
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Amyloid beta-Peptides / metabolism
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Amyloid beta-Peptides / toxicity*
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Astrocytes / cytology
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Astrocytes / drug effects
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Astrocytes / metabolism
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Cells, Cultured
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Coculture Techniques
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Dose-Response Relationship, Drug
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Endothelial Cells / cytology
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Endothelial Cells / drug effects
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Endothelial Cells / metabolism
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Endothelium, Vascular / drug effects*
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Endothelium, Vascular / metabolism
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Endothelium, Vascular / pathology
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Epidermal Growth Factor / pharmacology*
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Humans
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Microvessels / drug effects*
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Microvessels / metabolism
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Microvessels / pathology
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Models, Biological*
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Neovascularization, Physiologic / drug effects*
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Peptide Fragments / metabolism
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Peptide Fragments / toxicity*
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Pericytes / cytology
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Pericytes / drug effects
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Pericytes / metabolism
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Protein Multimerization
Substances
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Amyloid beta-Peptides
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Peptide Fragments
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amyloid beta-protein (1-42)
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Epidermal Growth Factor