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.
Mackic, Jasmina B.
McComb, J. Gordon
Kim, Kwang Sik
Yan, Shirley ShiDu
Stern, David M.
Schmidt, Ann Marie
Zlokovic, Berislav V.
American Society for Clinical Investigation
Scholarly/refereed, publisher version
MetadataShow full item record
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.
This is the published version. Copyright 1998 by American Society for Clinical Investigation.
- Pharmacy Scholarly Works 
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.
Items in KU ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
We want to hear from you! Please share your stories about how Open Access to this item benefits YOU.