N-terminal EFRH sequence of Alzheimer's beta-amyloid peptide represents the epitope of its anti-aggregating antibodies

Abstract

Monoclonal antibodies 6C6 and 10D5 raised against the N-terminal of beta-amyloid peptide interfere with the formation of beta-amyloid and trigger reversal to its non-toxic components. The epitopes of these antibodies were localized employing a library composed of filamentous phage displaying random combinatorial hexapeptides. Among 44 positive phage-clones, selected from the library by both antibodies, 40 clones carried the consensus sequence EFRH. These EFRH phage-clones bind specifically mAbs 6C6 or 10D5 with an apparent binding constant of approximately 10(-9) M. The peptide EFRH inhibits binding of mAbs 6C6 or 10D5 to beta-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 positions 3-6 within beta-amyloid peptide represents the sequential epitope of mAbs 6C6 and 10D5.