dc.contributor.author | Mackic, Jasmina B. | |
dc.contributor.author | Stins, Monique | |
dc.contributor.author | McComb, J. Gordon | |
dc.contributor.author | Calero, Miguel | |
dc.contributor.author | Ghiso, Jorge | |
dc.contributor.author | Kim, Kwang Sik | |
dc.contributor.author | Yan, Shirley ShiDu | |
dc.contributor.author | Stern, David M. | |
dc.contributor.author | Schmidt, Ann Marie | |
dc.contributor.author | Frangione, Blas | |
dc.contributor.author | Zlokovic, Berislav V. | |
dc.date.accessioned | 2015-05-28T14:39:46Z | |
dc.date.available | 2015-05-28T14:39:46Z | |
dc.date.issued | 1998-08-15 | |
dc.identifier.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. | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/17859 | |
dc.description | This is the published version. Copyright 1998 by American Society for Clinical Investigation. | en_US |
dc.description.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. | en_US |
dc.publisher | American Society for Clinical Investigation | en_US |
dc.title | 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. | en_US |
dc.type | Article | |
kusw.kuauthor | Yan, Shirley ShiDu | |
kusw.kudepartment | Pharmacology & Toxicology | en_US |
dc.identifier.doi | 10.1172/JCI2029 | |
kusw.oaversion | Scholarly/refereed, publisher version | |
kusw.oapolicy | This item does not meet KU Open Access policy criteria. | |
dc.rights.accessrights | openAccess | |