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

Rashid Deane, 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 HofmanMark Kindy, David Stern, Berislav Zlokovic

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)907-913
Number of pages7
JournalNature Medicine
Volume9
Issue number7
DOIs
StatePublished - Jul 1 2003
Externally publishedYes

Fingerprint

Blood-Brain Barrier
Amyloid
Brain
Peptides
Blood Vessels
Cerebrovascular Circulation
Bearings (structural)
Endothelin-1
Vasoconstriction
Transgenic Mice
Dementia
Blood
Cytokines
Ligands
Advanced Glycosylation End Product-Specific Receptor

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Deane, R., Yan, S. D., Submamaryan, R. K., LaRue, B., Jovanovic, S., Hogg, E., ... Zlokovic, B. (2003). RAGE mediates amyloid-β peptide transport across the blood-brain barrier and accumulation in brain. Nature Medicine, 9(7), 907-913. https://doi.org/10.1038/nm890

RAGE mediates amyloid-β peptide transport across the blood-brain barrier and accumulation in brain. / Deane, Rashid; Yan, Shi Du; 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.

In: Nature Medicine, Vol. 9, No. 7, 01.07.2003, p. 907-913.

Research output: Contribution to journalArticle

Deane, R, Yan, SD, 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 & Zlokovic, B 2003, 'RAGE mediates amyloid-β peptide transport across the blood-brain barrier and accumulation in brain', Nature Medicine, vol. 9, no. 7, pp. 907-913. https://doi.org/10.1038/nm890
Deane R, Yan SD, Submamaryan RK, LaRue B, Jovanovic S, Hogg E et al. RAGE mediates amyloid-β peptide transport across the blood-brain barrier and accumulation in brain. Nature Medicine. 2003 Jul 1;9(7):907-913. https://doi.org/10.1038/nm890
Deane, Rashid ; Yan, Shi Du ; 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. / RAGE mediates amyloid-β peptide transport across the blood-brain barrier and accumulation in brain. In: Nature Medicine. 2003 ; Vol. 9, No. 7. pp. 907-913.
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