N-TERMINAL EFRH SEQUENCE OF ALZHEIMERS BETA-AMYLOID PEPTIDE REPRESENTS THE EPITOPE OF ITS ANTI-AGGREGATING ANTIBODIES

Monoclonal antibodies 6C6 and 10D5 raised against the N-terminal of be ta-amyloid peptide interfere with the formation of beta-amyloid and tr igger reversal to its non-toxic components. The epitopes of these anti bodies were localized employing a library composed of filamentous phag e displaying random combinatorial hexapeptides. Among 44 positive phag e-clones, selected from the library by both antibodies, 40 clones carr ied the consensus sequence EFRH. These EFRH phage-clones bind specific ally mAbs 6C6 or 10D5 with an apparent binding constant of similar to 10(-9) M. The peptide EFRH inhibits binding of mAbs 6C6 or 10D5 to bet a-amyloid peptide in affinities identical to those obtained. with the peptides corresponding to positions 1-9, 1-16 and 1-40 of beta-peptide . These findings confirm that the peptide EFRH which is located at pos itions 3-6 within beta-amyloid peptide represents the sequential epito pe of mAbs 6C6 and 10D5. (C) 1998 Elsevier Science B.V. All rights res erved.