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- Title
RAGE mediates amyloid-B peptide transport across the blood-brain barrier and accumulation in brain.
- 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
- Abstract
Amyloid-β peptide (Aβ) interacts with the vasculature to influence Aβ levels in the brain and cerebral blood flow, providing a means of amplifying the Aβ-induced cellular stress underlying neuronal dysfunction and dementia. Systemic Aβ infusion and studies in genetically manipulated mice show that Aβ interaction with receptor for advanced glycation end products (RAGE)-bearing cells in the vessel wall results in transport of Aβ across the blood-brain barrier (BBB) and expression of proinflammatory cytokines and endothelin-1 (ET-1), the latter mediating Aβ-induced vasoconstriction. Inhibition of RAGE-ligand interaction suppresses accumulation of Aβ in brain parenchyma in a mouse transgenic model. These findings suggest that vascular RAGE is a target for inhibiting pathogenic consequences of Aβ-vascular interactions, including development of cerebral amyloidosis.
- Subjects
AMYLOID beta-protein; BLOOD-brain barrier; CEREBRAL circulation; MICE physiology
- Publication
Nature Medicine, 2003, Vol 9, Issue 7, p907
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/nm890