Background: In vivo administration of antibodies against the amyloid-β (Aβ) peptide has been shown to reduce and reverse the progressive amyloidosis that develops in a variety of mouse models of Alzheimer’s disease (AD). This work has been extended to clinical trials where subsequent autopsy cases of AD subjects immunized against Aβ showed similar reductions in parenchymal amyloid plaques, suggesting this approach to reduce neuropathology in man is feasible. Objective: Multiple hypotheses have been advanced to explain how anti-Aβ antibodies may lower amyloid burden. In this report, we compare approaches utilizing either plaque-binding or peptide-capturing anti-Aβ antibodies for effectiveness in reducing amyloidosis in a mouse model of AD. Methods: A plaque-binding monoclonal antibody (3D6) and an Aβ peptide-capturing monoclonal antibody (266) were compared in chronic treatment and prevention paradigms using a transgenic mouse model of AD. The effects of antibody therapy on plaque burden and plasma clearance of Aβ were investigated by quantitative imaging and clearance studies of intravenously injected 125I-Aβ. Results: The plaque-binding antibody 3D6 was highly effective in either treatment or prevention of amyloidosis. In these studies, the peptide-capture antibody 266 showed no reduction in amyloidosis in either paradigm and showed trends towards increasing amyloidosis. Antibody 266 was also found to greatly prolong (>180-fold) the normally rapid peripheral clearance of Aβ, in contrast to that found with 3D6 (>24-fold). Conclusion: Reversing and preventing Alzheimer’s type amyloidosis is most effectively accomplished with anti-amyloid antibodies that avidly bind plaque.

Keywords:
Immunotherapy, Alzheimer’s disease, Amyloid-β
This content is only available via PDF.
© 2008 S. Karger AG, Basel
2008
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.