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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.
MedLine Citation:
PMID:  21418385     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Objective:  To investigate the role of the receptor for advanced glycation end products (RAGE) in the epitope-dependent effects of beta-amyloid (Aβ) antibodies used as a peripheral sink therapy in Alzheimer's disease. Methods:  An in vitro model of the blood-brain barrier (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 of 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:
Corbin J Bachmeier; David Beaulieu-Abdelahad; Michael J Mullan; Daniel Paris
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-8
Journal Detail:
Title:  Microcirculation (New York, N.Y. : 1994)     Volume:  -     ISSN:  1549-8719     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-3-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9434935     Medline TA:  Microcirculation     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 John Wiley & Sons Ltd.
Affiliation:
The Roskamp Institute, 2040 Whitfield Avenue, Sarasota, Florida 34243, USA.
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