RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain |
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| Authors: | Deane Rashid Du Yan Shi Submamaryan Ram Kumar LaRue Barbara Jovanovic Suzana Hogg Elizabeth Welch Deborah Manness Lawrence Lin Chang Yu Jin Zhu Hong Ghiso Jorge Frangione Blas Stern Alan Schmidt Ann Marie Armstrong Don L Arnold Bernd Liliensiek Birgit Nawroth Peter Hofman Florence Kindy Mark Stern David Zlokovic Berislav |
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| Institution: | Frank P. Smith Laboratories for Neurosurgery, Department of Neurosurgery and Division of Neurovascular Biology, Center for Aging and Developmental Biology, University of Rochester Medical Center, Rochester, New York 14642, USA. |
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| Abstract: | Amyloid-beta peptide (Abeta) interacts with the vasculature to influence Abeta levels in the brain and cerebral blood flow, providing a means of amplifying the Abeta-induced cellular stress underlying neuronal dysfunction and dementia. Systemic Abeta infusion and studies in genetically manipulated mice show that Abeta interaction with receptor for advanced glycation end products (RAGE)-bearing cells in the vessel wall results in transport of Abeta across the blood-brain barrier (BBB) and expression of proinflammatory cytokines and endothelin-1 (ET-1), the latter mediating Abeta-induced vasoconstriction. Inhibition of RAGE-ligand interaction suppresses accumulation of Abeta in brain parenchyma in a mouse transgenic model. These findings suggest that vascular RAGE is a target for inhibiting pathogenic consequences of Abeta-vascular interactions, including development of cerebral amyloidosis. |
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