title: RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain.
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.
authors.affiliation: 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.
authors.forename: Rashid
authors.initials: R
authors.lastname: Deane
authors.forename: Shi
authors.initials: S
authors.lastname: Du Yan
authors.forename: Ram Kumar
authors.initials: RK
authors.lastname: Submamaryan
authors.forename: Barbara
authors.initials: B
authors.lastname: LaRue
authors.forename: Suzana
authors.initials: S
authors.lastname: Jovanovic
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hogg
authors.forename: Deborah
authors.initials: D
authors.lastname: Welch
authors.forename: Lawrence
authors.initials: L
authors.lastname: Manness
authors.forename: Chang
authors.initials: C
authors.lastname: Lin
authors.forename: Jin
authors.initials: J
authors.lastname: Yu
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
authors.forename: Jorge
authors.initials: J
authors.lastname: Ghiso
authors.forename: Blas
authors.initials: B
authors.lastname: Frangione
authors.forename: Alan
authors.initials: A
authors.lastname: Stern
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Schmidt
authors.forename: Don L
authors.initials: DL
authors.lastname: Armstrong
authors.forename: Bernd
authors.initials: B
authors.lastname: Arnold
authors.forename: Birgit
authors.initials: B
authors.lastname: Liliensiek
authors.forename: Peter
authors.initials: P
authors.lastname: Nawroth
authors.forename: Florence
authors.initials: F
authors.lastname: Hofman
authors.forename: Mark
authors.initials: M
authors.lastname: Kindy
authors.forename: David
authors.initials: D
authors.lastname: Stern
authors.forename: Berislav
authors.initials: B
authors.lastname: Zlokovic
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D021381:Protein Transport / Q000502:physiology; D000067759:Receptor for Advanced Glycation End Products; D044022:Receptor, Endothelin A; D011971:Receptors, Immunologic / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D016207:Cytokines; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D010446:Peptide Fragments; D000067759:Receptor for Advanced Glycation End Products; D044022:Receptor, Endothelin A; D011971:Receptors, Immunologic; C087220:BQ 610