title: Epitope-dependent effects of Beta-amyloid antibodies on Beta-amyloid clearance in an in vitro model of the blood-brain barrier.
abstract: OBJECTIVE
  To investigate the role of RAGE in the epitope-dependent effects of Aβ antibodies used as a peripheral sink therapy in AD.
  
  
  METHODS
  An in vitro model of the BBB was used to examine the effect of various Aβ antibodies or Aβ peptide fragments on Aβ exchange across the BBB.
  
  
  RESULTS
  An N-terminal Aβ antibody significantly enhanced the basolateral-to-apical transcytosis of fluorescein-Aβ(1-42) across the BBB model (41%), while no effect was apparent with a C-terminal Aβ antibody. Interestingly, modulation of RAGE in the presence of a C-terminal Aβ antibody resulted in a 65% increase in Aβ clearance across the BBB model, suggesting the C-terminal antibody-Aβ complex is susceptible to RAGE transport. Additionally, N-terminal peptide fragments of Aβ attenuated the brain penetration of full length Aβ in the BBB model, indicating the N-terminal region of Aβ is required for brain uptake.
  
  
  CONCLUSIONS
  Antibodies masking the N-terminal region of Aβ increase Aβ clearance across the BBB by preventing Aβ from interacting with the RAGE transporter, whereas antibodies bound to the C-terminus of Aβ are taken up by RAGE and, hence, do not influence the BBB clearance of Aβ.
authors.affiliation: The Roskamp Institute, Sarasota, Florida, USA. cbachmeier@rfdn.org
authors.forename: Corbin J
authors.initials: CJ
authors.lastname: Bachmeier
authors.forename: David
authors.initials: D
authors.lastname: Beaulieu-Abdelahad
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mullan
authors.forename: Daniel
authors.initials: D
authors.lastname: Paris
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000276:immunology / Q000378:metabolism*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000276:immunology / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects / Q000276:immunology; D001812:Blood-Brain Barrier / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D000939:Epitopes / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D017434:Protein Structure, Tertiary; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism; D057900:Transcytosis / Q000187:drug effects*
chemical_list: D016229:Amyloid beta-Peptides; D058846:Antibodies, Monoclonal, Murine-Derived; D000939:Epitopes; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic