RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain

Nat Med. 2003 Jul;9(7):907-13. doi: 10.1038/nm890.


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 types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Peptides / pharmacology
  • Animals
  • Blood-Brain Barrier / physiology*
  • Brain / blood supply
  • Brain / metabolism*
  • Cerebrovascular Circulation
  • Cytokines / genetics
  • Cytokines / metabolism
  • Endothelin Receptor Antagonists
  • Endothelin-1 / drug effects
  • Endothelin-1 / metabolism
  • Humans
  • Mice
  • Mice, Transgenic
  • Oligopeptides / pharmacology
  • Peptide Fragments / pharmacology
  • Protein Transport / physiology
  • Receptor for Advanced Glycation End Products
  • Receptor, Endothelin A
  • Receptors, Immunologic / metabolism*


  • Amyloid beta-Peptides
  • Cytokines
  • Endothelin Receptor Antagonists
  • Endothelin-1
  • Oligopeptides
  • Peptide Fragments
  • Receptor for Advanced Glycation End Products
  • Receptor, Endothelin A
  • Receptors, Immunologic
  • BQ 610