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.
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This work was supported by grants from the US Public Health Service (AG16223 and NS34467). R.D., S.D.Y. and R.S.K. contributed equally to this work. D.S. and M.K. were cosenior authors and B.V.Z. was a senior author.
The authors declare no competing financial interests.
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Deane, R., Du Yan, S., Submamaryan, R. et al. RAGE mediates amyloid-β peptide transport across the blood-brain barrier and accumulation in brain. Nat Med 9, 907–913 (2003). https://doi.org/10.1038/nm890
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