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.
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
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Brain Pathology | 2008 |
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The American Journal of Pathology | 2008 |
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Journal of Neuropathology and Experimental Neurology | 2008 |
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Drug Addiction
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Experimental Cell Research | 2006 |
Transport pathways for clearance of human Alzheimer's amyloid beta-peptide and apolipoproteins E and J in the mouse central nervous system
RD Bell, AP Sagare, AE Friedman, GS Bedi, DM Holtzman, R Deane, BV Zlokovic |
Journal of Cerebral Blood Flow & Metabolism | 2006 |
Major Involvement of Low-Density Lipoprotein Receptor-Related Protein 1 in the Clearance of Plasma Free Amyloid β-Peptide by the Liver
C Tamaki, S Ohtsuki, T Iwatsubo, T Hashimoto, K Yamada, C Yabuki, T Terasaki |
Pharmaceutical Research | 2006 |
Mechanism of Cerebral β-Amyloid Angiopathy: Murine and Cellular Models
MC Herzig, WE Nostrand, M Jucker |
Brain Pathology | 2006 |
The −374 T/A polymorphism in the gene encoding RAGE is associated with diabetic nephropathy and retinopathy in type 1 diabetic patients
E Lindholm, E Bakhtadze, M Sjögren, CM Cilio, E Agardh, L Groop, CD Agardh |
Diabetologia | 2006 |
CNS drug delivery: Opioid peptides and the blood-brain barrier
KA Witt, TP Davis |
The AAPS Journal | 2006 |
RAGE, LRP-1, and amyloid-beta protein in Alzheimer’s disease
JE Donahue, SL Flaherty, CE Johanson, JA Duncan, GD Silverberg, MC Miller, R Tavares, W Yang, Q Wu, E Sabo, V Hovanesian, EG Stopa |
Acta Neuropathologica | 2006 |
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HP Schmitt |
Medical Hypotheses | 2006 |
Understanding RAGE, the receptor for advanced glycation end products
A Bierhaus, PM Humpert, M Morcos, T Wendt, T Chavakis, B Arnold, DM Stern, PP Nawroth |
Journal of Molecular Medicine | 2005 |
Evaluation of rage isoforms, ligands, and signaling in the brain
Q Ding, JN Keller |
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research | 2005 |
Colloidal carriers and blood–brain barrier (BBB) translocation: A way to deliver drugs to the brain?
E Garcia-Garcia, K Andrieux, S Gil, P Couvreur |
International Journal of Pharmaceutics | 2005 |
Permeability Studies on In Vitro Blood–Brain Barrier Models: Physiology, Pathology, and Pharmacology
MA Deli, CS Ábrahám, Y Kataoka, M Niwa |
Cellular and Molecular Neurobiology | 2005 |
Role of the MEOX2 homeobox gene in neurovascular dysfunction in Alzheimer disease
Z Wu, H Guo, N Chow, J Sallstrom, RD Bell, R Deane, AI Brooks, S Kanagala, A Rubio, A Sagare, D Liu, F Li, D Armstrong, T Gasiewicz, R Zidovetzki, X Song, F Hofman, BV Zlokovic |
Nature Medicine | 2005 |
International Review of Neurobiology
ZT Bloomgarden |
International review of neurobiology | 2005 |
The Blood-Brain Barrier and Its Microenvironment: Basic Physiology to Neurological Disease
H Wolburg, A Warth |
The Blood-Brain Barrier and Its Microenvironment: Basic Physiology to Neurological Disease | 2005 |
The choroid plexus removes beta-amyloid from brain cerebrospinal fluid
JS Crossgrove, GJ Li, W Zheng |
Experimental biology and medicine (Maywood, N.J.) | 2005 |
RAGE and amyloid beta interactions: Atomic force microscopy and molecular modeling
MO Chaney, WB Stine, TA Kokjohn, YM Kuo, C Esh, A Rahman, DC Luehrs, AM Schmidt, D Stern, SD Yan, AE Roher |
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | 2005 |
The Choroid Plexus Removes β-Amyloid from Brain Cerebrospinal Fluid
JS Crossgrove, GJ Li, W Zheng |
Experimental biology and medicine (Maywood, N.J.) | 2005 |
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GM Bishop, SR Robinson |
Drugs & Aging | 2004 |
LRP/Amyloid β-Peptide Interaction Mediates Differential Brain Efflux of Aβ Isoforms
R Deane, Z Wu, A Sagare, J Davis, SD Yan, K Hamm, F Xu, M Parisi, B LaRue, HW Hu, P Spijkers, H Guo, X Song, PJ Lenting, WE van Nostrand, BV Zlokovic |
Neuron | 2004 |
Method for measurement of the blood–brain barrier permeability in the perfused mouse brain: application to amyloid-β peptide in wild type and Alzheimer’s Tg2576 mice
B LaRue, E Hogg, A Sagare, S Jovanovic, L Maness, C Maurer, R Deane, BV Zlokovic |
Journal of Neuroscience Methods | 2004 |
Blood-Spinal Cord and Brain Barriers in Health and Disease
E Anderson, L Ryan, H Xiong, S Swindells, J Zheng, HE Gendelman |
Blood-Spinal Cord and Brain Barriers in Health and Disease | 2004 |
Peripheral treatment with enoxaparin, a low molecular weight heparin, reduces plaques and beta-amyloid accumulation in a mouse model of Alzheimer's disease
L Bergamaschini, E Rossi, C Storini, S Pizzimenti, M Distaso, C Perego, AD Luigi, C Vergani, MG de Simoni |
The Journal of neuroscience : the official journal of the Society for Neuroscience | 2004 |
Systemic Catabolism of Alzheimer's Aβ40 and Aβ42
J Ghiso, M Shayo, M Calero, D Ng, Y Tomidokoro, S Gandy, A Rostagno, B Frangione |
The Journal of biological chemistry | 2004 |
Amyloid β(1–42) and its β(25–35) fragment induce activation and membrane translocation of cytosolic phospholipase A2 in bovine retina capillary pericytes
CD Anfuso, G Assero, G Lupo, A Nicotra, G Cannavò, RP Strosznajder, P Rapisarda, R Pluta, M Alberghina |
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | 2004 |
RAGE mediates amyloid-β peptide transport across the blood-brain barrier and accumulation in brain
R Deane, SD Yan, RK Submamaryan, B LaRue, S Jovanovic, E Hogg, D Welch, L Manness, C Lin, J Yu, H Zhu, J Ghiso, B Frangione, A Stern, AM Schmidt, DL Armstrong, B Arnold, B Liliensiek, P Nawroth, F Hofman, M Kindy, D Stern, B Zlokovic |
Nature Medicine | 2003 |
International Textbook of Diabetes Mellitus
RA DeFronzo, L Mandarino, E Ferrannini |
International Textbook of Diabetes Mellitus | 2003 |
THEROLE OFDRUGTRANSPORTERS AT THEBLOOD-BRAINBARRIER
AG Boer, IC der Sandt, PJ Gaillard |
Annual Review of Pharmacology and Toxicology | 2003 |
A simple method for isolation and characterization of mouse brain microvascular endothelial cells
Z Wu, FM Hofman, BV Zlokovic |
Journal of Neuroscience Methods | 2003 |
Alzheimer’s Disease
DS Vohora, LC Mishra |
Scientific Basis for Ayurvedic Therapies | 2003 |
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AG Boer, IC der Sandt, PJ Gaillard |
Annual Review of Pharmacology and Toxicology | 2003 |
Transcytosis: Crossing Cellular Barriers
PL Tuma, AL Hubbard |
Physiological reviews | 2003 |
Activated protein C blocks p53-mediated apoptosis in ischemic human brain endothelium and is neuroprotective
T Cheng, D Liu, JH Griffin, JA Fernández, F Castellino, ED Rosen, K Fukudome, BV Zlokovic |
Nature Medicine | 2003 |
Amyloid Peptide-Induced Cytokine and Chemokine Expression in THP-1 Monocytes Is Blocked by Small Inhibitory RNA Duplexes for Early Growth Response-1 Messenger RNA
RK Giri, SK Selvaraj, VK Kalra |
Journal of immunology (Baltimore, Md. : 1950) | 2003 |
Sporadic and Familial Cerebral Amyloid Angiopathies
T Revesz, JL Holton, T Lashley, G Plant, A Rostagno, J Ghiso, B Frangione |
Brain Pathology | 2002 |
Human antibodies against amyloid β peptide: A potential treatment for Alzheimer's disease: Human Antibodies against Amyloid β Peptide
R Dodel, H Hampel, C Depboylu, S Lin, F Gao, S Schock, S Jäckel, X Wei, K Buerger, C Höft, B Hemmer, HJ Möller, M Farlow, WH Oertel, N Sommer, Y Du |
Annals of Neurology | 2002 |
Circulating amyloid-β peptide crosses the blood–brain barrier in aged monkeys and contributes to Alzheimer's disease lesions
JB Mackic, J Bading, J Ghiso, L Walker, T Wisniewski, B Frangione, BV Zlokovic |
Vascular Pharmacology | 2002 |
Cyclooxygenase-2-positive macrophages infiltrate the Alzheimer's disease brain and damage the blood-brain barrier
M Fiala, QN Liu, J Sayre, V Pop, V Brahmandam, MC Graves, HV Vinters |
European Journal of Clinical Investigation | 2002 |
Heparin attenuates cytotoxic and inflammatory activity of Alzheimer amyloid-β in vitro
L Bergamaschini, C Donarini, E Rossi, AD Luigi, C Vergani, MG de Simoni |
Neurobiology of Aging | 2002 |
Intracellular accumulation of β-amyloid1–42 in neurons is facilitated by the α7 nicotinic acetylcholine receptor in Alzheimer’s disease
RG Nagele, MR D’Andrea, WJ Anderson, HY Wang |
Neuroscience | 2002 |
Universes in Delicate Balance
RH Miller, S Robinson |
Universes in Delicate Balance | 2002 |
BSE: a consequence of cattle feeding with glycated molecules host-unknown?
J Boratyński, A Górski |
Medical Hypotheses | 2002 |
Aβ 42 -induced Increase in Neprilysin Is Associated with Prevention of Amyloid Plaque Formation in Vivo
MH Mohajeri, MA Wollmer, RM Nitsch |
The Journal of biological chemistry | 2002 |
Antibodies to β-Amyloid Decrease the Blood-to-Brain Transfer of β-Amyloid Peptide 1
W Pan, B Solomon, LM Maness, AJ Kastin |
Experimental biology and medicine (Maywood, N.J.) | 2002 |
Diabetes and advanced glycation endproducts
H Vlassara, MR Palace |
Journal of Internal Medicine | 2002 |
Effect of endothelial cell polarity on β-amyloid-induced migration of monocytes across normal and AD endothelium
R Giri, S Selvaraj, CA Miller, F Hofman, SD Yan, D Stern, BV Zlokovic, VK Kalra |
American journal of physiology. Cell physiology | 2002 |
Noninvasive Imaging of Peripherally Injected Alzheimer's Disease Type Synthetic Aβ Amyloid In Vivo
JR Marshall, ER Stimson, JR Ghilardi, HV Vinters, PW Mantyh, JE Maggio |
Bioconjugate Chemistry | 2002 |
The AGE-receptor in the pathogenesis of diabetic complications
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Diabetes/Metabolism Research and Reviews | 2001 |
Peptide drug modifications to enhance bioavailability and blood-brain barrier permeability
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α2-Macroglobulin-Mediated Degradation of Amyloid β1–42: A Mechanism to Enhance Amyloid β Catabolism
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Experimental Neurology | 2001 |
Bacterial invasion and transcytosis in transfected human brain microvascular endothelial cells
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Microbial Pathogenesis | 2001 |
Neuroinflammatory Mechanisms in Alzheimer’s Disease Basic and Clinical Research
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The chemokine receptor CCR2 mediates the binding and internalization of monocyte chemoattractant protein-1 along brain microvessels
K A Dzenko, A V Andjelkovic, W A Kuziel, J S Pachter |
The Journal of neuroscience : the official journal of the Society for Neuroscience | 2001 |
The Chemokine Receptor CCR2 Mediates the Binding and Internalization of Monocyte Chemoattractant Protein-1 along Brain Microvessels
Dzenko KA, Andjelkovic AV, Kuziel WA, Pachter JS |
Journal of Neuroscience | 2001 |
Clearance of Alzheimer's amyloid beta1-40 peptide from brain by low-density lipoprotein receptor-related protein-1 at the blood-brain barrier
Masayoshi Shibata, Shinya Yameda,Ram Kumar, Miguel Calero,ar, James Bading, Blas Frangione, David Holtzman, Carol A. Miller, Dudley K. Strickland,Jorge Ghiso, Berislav V. Zlokovic |
Journal of Clinical Investigation | 2000 |
Apolipoprotein J (clusterin) and Alzheimer's disease
M Calero, A Rostagno, E Matsubara, B Zlokovic, B Frangione, J Ghiso |
Microscopy Research and Technique | 2000 |
Mechanisms of Cerebrovascular Amyloid Deposition: Lessons from Mouse Models
P Burgermeister, ME Calhoun, DT Winkler, M Jucker |
Annals of the New York Academy of Sciences | 2000 |
Improved bioavailability to the brain of glycosylated Met-enkephalin analogs
RD Egleton, SA Mitchell, JD Huber, J Janders, D Stropova, R Polt, HI Yamamura, VJ Hruby, TP Davis |
Brain Research | 2000 |
The biology of the receptor for advanced glycation end products and its ligands
A M Schmidt, S D Yan, S F Yan, D M Stern |
Biochimica et Biophysica Acta | 2000 |
Cellular cofactors potentiating induction of stress and cytotoxicity by amyloid beta-peptide
S D Yan, A Roher, M Chaney, B Zlokovic, A M Schmidt, D Stern |
Biochimica et Biophysica Acta | 2000 |
β-Amyloid-induced migration of monocytes across human brain endothelial cells involves RAGE and PECAM-1
R Giri, Y Shen, M Stins, SD Yan, AM Schmidt, D Stern, KS Kim, B Zlokovic, VK Kalra |
American journal of physiology. Cell physiology | 2000 |
Clearance of amyloid β-peptide from brain: transport or metabolism?
BV Zlokovic, S Yamada, D Holtzman, J Ghiso, B Frangione |
Nature Medicine | 2000 |
Differential Regulation of Leptin Transport by the Choroid Plexus and Blood-Brain Barrier and High Affinity Transport Systems for Entry into Hypothalamus and Across the Blood-Cerebrospinal Fluid Barrier*
BV Zlokovic, S Jovanovic, W Miao, S Samara, S Verma, CL Farrell |
Endocrinology | 2000 |
Reply to: 'Clearance of amyloid β-peptide from brain: transport or metabolism?'
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Nature Medicine | 2000 |
Cerebral Amyloid Angiopathy in Alzheimer’s Disease and Related Disorders
MM Verbeek, RM de Waal, HV Vinters |
2000 | |
Pentosan polysulfate regulates scavenger receptor-mediated, but not fluid-phase, endocytosis in immortalized cerebral endothelial cells
M A Deli, C S Abrahám, H Takahata, S Katamine, M Niwa |
Cellular and Molecular Neurobiology | 2000 |
Cellular Cofactors for Amyloid β-Peptide-Induced Cell Stress
SD Yan, A Roher, AM Schmidt, DM Stern |
The American Journal of Pathology | 1999 |
Cellular cofactors for amyloid beta-peptide-induced cell stress. Moving from cell culture to in vivo
SD Yan, A Roher, AM Schmidt, DM Stern |
The American Journal of Pathology | 1999 |
RAGE Mediates a Novel Proinflammatory Axis
MA Hofmann, S Drury, C Fu, W Qu, A Taguchi, Y Lu, C Avila, N Kambham, A Bierhaus, P Nawroth, MF Neurath, T Slattery, D Beach, J McClary, M Nagashima, J Morser, D Stern, AM Schmidt |
Cell | 1999 |
The evolution of Alzheimer disease, the reproductive schedule, and apoE isoforms☆
CE Finch, RM Sapolsky |
Neurobiology of Aging | 1999 |
Neuroprotective approaches in experimental models of β-Amyloid neurotoxicity: Relevance to Alzheimer's disease
T Harkany, T Hortobágyi, M Sasvári, C Kónya, B Penke, PG Luiten, N Csaba |
Progress in Neuro-Psychopharmacology and Biological Psychiatry | 1999 |
cDNA cloning of a novel secreted isoform of the human receptor for advanced glycation end products and characterization of cells co-expressing cell-surface scavenger receptors and Swedish mutant amyloid precursor protein
P Malherbe, JG Richards, H Gaillard, A Thompson, C Diener, A Schuler, G Huber |
Molecular Brain Research | 1999 |
Cereport (RMP-7) increases the permeability of human brain microvascular endothelial cell monolayers
J B Mackic, M Stins, S Jovanovic, K S Kim, R T Bartus, B V Zlokovic |
Pharmaceutical Research | 1999 |