Vaccination for the prevention and treatment of Alzheimer's disease

In vitro studies showed that beta-amyloid peptide neurotoxicity correlates with the formation of fibrillar beta-amyloid and the variation in neurotoxi c potency is related to the extent of peptide aggregation. Many efforts are being focused on the development of potent and selective inhibitors of amy loid formation in order to reduce the extent of their deposition and relate d neurotoxic effects. In our laboratory we are pioneering the idea that sit e-directed monoclonal antibodies (MAbs) can solubilize synthetic beta-amylo id aggregates. Production and performance of such antibodies by repeated in jections of toxic human beta-amyloid fibrils into transgenic mice suggests the feasibility of vaccination against Alzheimer's disease (AD). Here we re port the development of a novel immunization procedure for the production o f effective antiaggregating beta-amyloid antibodies. The antigen is built f rom filamentous phages displaying the only four amino acids EFRH located at positions 3-6 of the beta-amyloid peptide found to be the main regulatory site of amyloid formation. Autoimmune antibodies are obtained by EFRH phage administration in guinea pigs, which exhibit human identity in the beta-am yloid peptide region. Availability of such antibodies opens up possibilitie s for the development of an efficient and long-lasting immunization procedu re for the treatment of AD. (C) 2000 Prous Science. All rights reserved.