The β-amyloid peptide, the hallmark of Alzheimer disease, forms fibrillar toxic aggregates in brain tissue that can be dissolved only by strung denaturing agents. To study β-amyloid formation and its inhibition, we prepared immune complexes with two monoclonal antibodies (mAbs), AMY-33 and 6F/3D, raised against β-amyloid fragments spanning amino acid residues 1-28 and 8-17 of the β-amyloid peptide chain, respectively. In vitro aggregation of β-amyloid peptide was induced by incubation fur 3 h at 37°C and monitored by ELISA, negative staining electron microscopy, and fluorimetric studies. We found that the mAbs prevent the aggregation of β-amyloid peptide and that the inhibitory effect appears to be related to the localization of the antibody-binding sites and the nature of the aggregating agents. Preparation of mAbs against 'aggregating epitopes,' defined as sequences related to the sites where protein aggregation is initiated, may lead to the understanding and prevention of protein aggregation. The results of this study may provide a foundation for using mAbs in vivo to prevent the β- amyloid peptide aggregation that is associated with Alzheimer disease.
|Number of pages||4|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - 9 Jan 1996|