Advertisement

Citations to this article

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.

Authors

J B Mackic, M Stins, J G McComb, M Calero, J Ghiso, K S Kim, S D Yan, D Stern, A M Schmidt, B Frangione, B V Zlokovic

×

Total citations by year

Year: 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 Total
Citations: 1 4 10 7 8 10 8 3 8 5 4 3 6 4 4 6 91
Citation information

Citations to this article in year 2012 (10)

Title and authors Publication Year
Aβ42 production in brain capillary endothelial cells after oxygen and glucose deprivation
A Bulbarelli, E Lonati, A Brambilla, A Orlando, E Cazzaniga, F Piazza, C Ferrarese, M Masserini, G Sancini
Molecular and Cellular Neuroscience 2012
A multimodal RAGE-specific inhibitor reduces amyloid β–mediated brain disorder in a mouse model of Alzheimer disease
R Deane, I Singh, AP Sagare, RD Bell, NT Ross, B LaRue, R Love, S Perry, N Paquette, RJ Deane, T Meenakshisundaram, T Zarcone, G Fritz, AE Friedman, BL Miller, BV Zlokovic
Journal of Clinical Investigation 2012
Is RAGE still a therapeutic target for Alzheimer’s disease?
RJ Deane
Future Medicinal Chemistry 2012
A multimodal RAGE-specific inhibitor reduces amyloid β–mediated brain disorder in a mouse model of Alzheimer disease
R Deane, I Singh, AP Sagare, RD Bell, NT Ross, B LaRue, R Love, S Perry, N Paquette, RJ Deane, M Thiyagarajan, T Zarcone, G Fritz, AE Friedman, BL Miller, BV Zlokovic
Journal of Clinical Investigation 2012
Microglial Scavenger Receptors and Their Roles in the Pathogenesis of Alzheimer's Disease
K Wilkinson, JE Khoury
International Journal of Alzheimer's Disease 2012
Low-density lipoprotein receptor-related protein 1: A physiological Aβ homeostatic mechanism with multiple therapeutic opportunities
AP Sagare, R Deane, BV Zlokovic
Pharmacology & Therapeutics 2012
Beta-Amyloid Monomer and Insulin/IGF-1 Signaling in Alzheimer's Disease
ML Giuffrida, F Tomasello, F Caraci, S Chiechio, F Nicoletti, A Copani
Molecular Neurobiology 2012
International Review of Neurobiology
SD Skaper
International review of neurobiology 2012
Cilostazol Strengthens Barrier Integrity in Brain Endothelial Cells
S Horai, S Nakagawa, K Tanaka, Y Morofuji, PO Couraud, MA Deli, M Ozawa, M Niwa
Cellular and Molecular Neurobiology 2012
Aβ-induced formation of autophagosomes is mediated by RAGE-CaMKKβ-AMPK signaling
SM Son, ES Jung, HJ Shin, J Byun, I Mook-Jung
Neurobiology of Aging 2012

Advertisement
Advertisement