RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain - PubMed (original) (raw)

Shi Du Yan, Ram Kumar Submamaryan, Barbara LaRue, Suzana Jovanovic, Elizabeth Hogg, Deborah Welch, Lawrence Manness, Chang Lin, Jin Yu, Hong Zhu, Jorge Ghiso, Blas Frangione, Alan Stern, Ann Marie Schmidt, Don L Armstrong, Bernd Arnold, Birgit Liliensiek, Peter Nawroth, Florence Hofman, Mark Kindy, David Stern, Berislav Zlokovic

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

Rashid Deane et al. Nat Med. 2003 Jul.

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.

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