We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
RAGE mediates amyloid-beta 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; Hofman, Florence; Kindy, Mark; Stern, David; Zlokovic, Berislav
- 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.
- Publication
Nature medicine, 2003, Vol 9, Issue 7, p907
- ISSN
1078-8956
- Publication type
Journal Article
- DOI
10.1038/nm890