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.

journal_name

Nat Med

journal_title

Nature medicine

authors

Deane R,Du Yan S,Submamaryan RK,LaRue B,Jovanovic S,Hogg E,Welch D,Manness L,Lin C,Yu J,Zhu H,Ghiso J,Frangione B,Stern A,Schmidt AM,Armstrong DL,Arnold B,Liliensiek B,Nawroth P,Hofman F,Kindy M,Stern D,Zlokov

doi

10.1038/nm890

keywords:

subject

Has Abstract

pub_date

2003-07-01 00:00:00

pages

907-13

issue

7

eissn

1078-8956

issn

1546-170X

pii

nm890

journal_volume

9

pub_type

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