High affinity binding of monoclonal antibodies to the sequential epitope EFRH of β-amyloid peptide is essential for modulation of fibrillar aggregation

Monoclonal antibodies raised against the N-terminal of Alzheimer's β- amyloid peptide (βAP) were found to modulate its fibrillar aggregation. While mAbs 6C6 and 10D5 inhibit the formation of β-amyloid fibrils, trigger disaggregation and reversal to its non-toxic form, mAb 2H3 is devoid of these properties. MAb 2H3 binds the sequence DAEFRHD, corresponding to position 1- 7 of the ∅P with high affinity (2 X 10^-9M) similar to its binding with the whole βAP. The EFRH peptide strongly inhibits binding of mAbs 6C6 and 10D5 to βAP, whereas it inhibits weakly the interaction of 2H3 with βAP. Low affinity binding of mAb 2H3 to EFRH might explain its failure in prevention of β-amyloid formation.