Cited by 1,426Alzheimer's disease research and treatmentsAdvanced Glycation End Products researchBarrier Structure and Function Studies

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

Deane, Rashid, Du Yan, Shi, Submamaryan, Ram Kumar, LaRue, Barbara, Jovanovic, Suzana, Hogg, Elizabeth, Welch, Deborah, Manness, Lawrence +15 more·2003·Nature Medicine

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.

Integrity signals

Registry

Crossref · 10.1038/nm890

Cites

47 of 47 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Under pathological conditions, RAGE mediates reentry or influx of circulating Aβ across the blood-brain barrier into the brain.

    “Under pathological conditions, RAGE mediates reentry or influx of circulating A 𝛃 across the BBB into the brain, which is associated with neuroinflammatory response, CBF reductions, and BBB breakdown (134, 136)”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [134]

  • RAGE-mediated reentry or influx of circulating Aβ across the blood-brain barrier is associated with neuroinflammatory response, cerebral blood flow reductions, and blood-brain barrier breakdown.

    “which is associated with neuroinflammatory response, CBF reductions, and BBB breakdown (134, 136)”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [134]

  • RAGE expression at the blood-brain barrier is increased in Alzheimer's disease and Alzheimer's disease models.

    “Its expression at the BBB is increased in AD and AD models (134, 152, 410).”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [134]

  • The receptor for advanced glycation end products (RAGE) is expressed mainly at the luminal membrane of the blood-brain barrier.

    “In contrast to lipoprotein receptors, the receptor for advanced glycation end products (RAGE) is expressed mainly at the luminal membrane of the BBB (134).”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [134]

  • RAGE expression is increased in Alzheimer's disease brain endothelium and mural cells.

    “In contrast to LRP1, expression of RAGE, a major A 𝛃 influx receptor, is increased in AD brain endothelium and mural cells (134, 152, 410)”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [134]

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. DeMattos, R.B. et al. Potential role of endogenous and exogenous Aβ binding molecules in Aβ clearance and metabolism. in Aβ Metabolism in Alzheimer's Disease (ed. Saido, T.) 123–139 (Landes Bioscience, Georgetown, Texas, 2003).

Cited by

Sorted by citations

Authors
Deane, R., Du Yan, S., Submamaryan, R. K., LaRue, B., Jovanovic, S., Hogg, E., Welch, D., Manness, L., Lin, C., Yu, J., Zhu, H., Ghiso, J., Frangione, B., Stern, A., Schmidt, A. M., Armstrong, D. L., Arnold, B., Liliensiek, B., Nawroth, P., Hofman, F., Kindy, M., Stern, D., & Zlokovic, B.
Affiliations
  • University of Rochester Medicine (US)
  • University of Southern California (US)
  • Columbia University (US)
  • University of Kentucky (US)
  • NYU Langone Health (US)
  • Heidelberg University (DE)
  • Augusta University (US)
Venue
Nature Medicine
Published
2003-06-15
Volume
9
Issue
7
Pages
907-913
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
OpenAlex
W2041851050
Cited by
1,426
References
47
Citations by year
2026: 52 · 2025: 60 · 2024: 56 · 2023: 74 · 2022: 77 · 2021: 88 · 2020: 89 · 2019: 68 · 2018: 68 · 2017: 68 · 2016: 69 · 2015: 76 · 2014: 70 · 2013: 60 · 2012: 72
FWCI
16.29
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute on Aging (AG16223)
  • National Institute of Neurological Disorders and Stroke (NS34467)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords
amyloid-beta, receptor for advanced glycation end products, RAGE, blood-brain barrier, amyloid-beta transport, cerebral amyloidosis, endothelin-1, vasoconstriction, inflammatory cytokines, Alzheimer's disease, dementia, cerebral blood flow
MeSH terms
Receptor for Advanced Glycation End Products, Aged, Aged, 80 and over, Animals, Blood-Brain Barrier, Brain, Cerebrovascular Circulation, Humans, Mice, Transgenic, Oligopeptides, Peptide Fragments, Receptors, Immunologic, Cytokines, Amyloid beta-Peptides, Endothelin-1, Protein Transport, Receptor, Endothelin A, Mice, Endothelin Receptor Antagonists

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review