MONOCLONAL-ANTIBODIES INHIBIT IN-VITRO FIBRILLAR AGGREGATION OF THE ALZHEIMER BETA-AMYLOID PEPTIDE

The beta-amyloid peptide, the hallmark of Alzheimer disease, forms fib rillar toxic aggregates in brain tissue that can be dissolved only by strong denaturing agents. To study beta-amyloid formation and its inhi bition, we prepared immune complexes with two monoclonal antibodies (m Abs), AMY-33 and 6F/3D, raised against beta-amyloid fragments spanning amino acid residues 1-28 and 8-17 of the beta-amyloid peptide chain, respectively. In vitro aggregation of beta-amyloid peptide was induced by incubation for 3 h at 37 degrees C and monitored by ELISA, negativ e staining electron microscopy, and fluorimetric studies, We found tha t the mAbs prevent the aggregation of beta-amyloid peptide and that th e inhibitory effect appears to be related to the localization of the a ntibody-binding sites and the nature of the aggregating agents, Prepar ation of mAbs against ''aggregating epitopes,'' defined as sequences r elated to the sites where protein aggregation is initiated, may lead t o the understanding and prevention of protein aggregation, The results of this study may provide a foundation for using mAbs in vivo to prev ent the beta-amyloid peptide aggregation that is associated with Alzhe imer disease.