In vitro studies showed that β-amyloid peptide neurotoxicity correlates with the formation of fibrillar β-amyloid and the variation in neurotoxic potency is related to the extent of peptide aggregation. Many efforts are being focused on the development of potent and selective inhibitors of amyloid formation in order to reduce the extent of their deposition and related neurotoxic effects. In our laboratory we are pioneering the idea that site-directed monoclonal antibodies (MAbs) can solubilize synthetic β-amyloid aggregates. Production and performance of such antibodies by repeated injections of toxic human β-amyloid fibrils into transgenic mice suggests the feasibility of vaccination against Alzheimer's disease (AD). Here we report the development of a novel immunization procedure for the production of effective antiaggregating β-amyloid antibodies. The antigen is built from filamentous phages displaying the only four amino acids EFRH located at positions 3-6 of the β-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 β-amyloid peptide region. Availability of such antibodies opens up possibilities for the development of an efficient and long-lasting immunization procedure for the treatment of AD. (C) 2000 Prous Science.