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Epitope‐Dependent Effects of Beta‐Amyloid Antibodies on Beta‐Amyloid Clearance in an In Vitro Model of the Blood–Brain Barrier
Author(s) -
BACHMEIER CORBIN J.,
BEAULIEUABDELAHAD DAVID,
MULLAN MICHAEL J.,
PARIS DANIEL
Publication year - 2011
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1111/j.1549-8719.2011.00096.x
Subject(s) - transcytosis , antibody , epitope , in vitro , blood–brain barrier , chemistry , peptide , amyloid beta , transporter , microbiology and biotechnology , immunology , biology , biochemistry , endocytosis , receptor , endocrinology , central nervous system , gene
Please cite this paper as: Bachmeier, Beaulieu‐Abdelahad, Mullan, and Paris (2011). Epitope‐Dependent Effects of Beta‐Amyloid Antibodies on Beta‐Amyloid Clearance in an In Vitro Model of the Blood–Brain Barrier. Microcirculation 18 (5), 373–379. 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.