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    Human blood-brain barrier receptors for Alzheimer's amyloid-beta 1- 40. Asymmetrical binding, endocytosis, and transcytosis at the apical side of brain microvascular endothelial cell monolayer.

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    YanShirley_JCI_102(4)734.pdf (550.4Kb)
    Issue Date
    1998-08-15
    Author
    Mackic, Jasmina B.
    Stins, Monique
    McComb, J. Gordon
    Calero, Miguel
    Ghiso, Jorge
    Kim, Kwang Sik
    Yan, Shirley ShiDu
    Stern, David M.
    Schmidt, Ann Marie
    Frangione, Blas
    Zlokovic, Berislav V.
    Publisher
    American Society for Clinical Investigation
    Type
    Article
    Article Version
    Scholarly/refereed, publisher version
    Metadata
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    Abstract
    A soluble monomeric form of Alzheimer's amyloid-beta (1-40) peptide (sAbeta1-40) is present in the circulation and could contribute to neurotoxicity if it crosses the brain capillary endothelium, which comprises the blood-brain barrier (BBB) in vivo. This study characterizes endothelial binding and transcytosis of a synthetic peptide homologous to human sAbeta1-40 using an in vitro model of human BBB. 125I-sAbeta1-40 binding to the brain microvascular endothelial cell monolayer was time dependent, polarized to the apical side, and saturable with high- and low-affinity dissociation constants of 7.8+/-1.2 and 52.8+/-6.2 nM, respectively. Binding of 125I-sAbeta1-40 was inhibited by anti-RAGE (receptor for advanced glycation end products) antibody (63%) and by acetylated low density lipoproteins (33%). Consistent with these data, transfected cultured cells overexpressing RAGE or macrophage scavenger receptor (SR), type A, displayed binding and internalization of 125I-sAbeta1-40. The internalized peptide remains intact > 94%. Transcytosis of 125I-sAbeta1-40 was time and temperature dependent, asymmetrical from the apical to basolateral side, saturable with a Michaelis constant of 45+/-9 nM, and partially sensitive to RAGE blockade (36%) but not to SR blockade. We conclude that RAGE and SR mediate binding of sAbeta1-40 at the apical side of human BBB, and that RAGE is also involved in sAbeta1-40 transcytosis.
    Description
    This is the published version. Copyright 1998 by American Society for Clinical Investigation.
    URI
    http://hdl.handle.net/1808/17859
    DOI
    https://doi.org/10.1172/JCI2029
    Collections
    • Pharmacy Scholarly Works [286]
    Citation
    Mackic, J. B., M. Stins, J. G. Mccomb, M. Calero, J. Ghiso, K. S. Kim, S. D. Yan, D. Stern, A. M. Schmidt, B. Frangione, and B. V. Zlokovic. "Human Blood-brain Barrier Receptors for Alzheimer's Amyloid-beta 1- 40. Asymmetrical Binding, Endocytosis, and Transcytosis at the Apical Side of Brain Microvascular Endothelial Cell Monolayer." Journal of Clinical Investigation J. Clin. Invest. 102.4 (1998): 734-43. http://dx.doi.org/10.1172/JCI2029.

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    KU Libraries
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    785-864-8983

    KU Libraries
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    Lawrence, KS 66045
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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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