Zinc binding agonist effect on the recognition of the β-amyloid (4–10) epitope by anti-β-amyloid antibodies

Abstract

Amyloid plaques associated to Alzheimer’s disease present a high content of zinc ions. We previously showed that the N-terminal region of the amyloid peptide Aβ constitutes an autonomous zinc-binding domain. This region encompasses the previously identified epitope Aβ(4–10) targeted by antibodies capable to reduce amyloid deposition, but the influence of Aβ/Zn binding on the epitope recognition remains unknown. We demonstrate here the effect of Zn2+ ions on the recognition of peptides sharing the sequence of the Aβ N-terminal domain, by two monoclonal antibodies recognizing the β-amyloid(4–10) epitope. The presence of Zn2+, but not of other cations, increased the recognition of the (1–16) peptide, while it was without effect on the recognition of the (1–10) peptide. These findings show a zinc-induced conformational change of the (1–16)-N-terminal region of Aβ, which results in a better accessibility of the Aβ(4–10) epitope to the anti-Aβ antibodies, and suggest a role of zinc in epitope-based vaccination approaches.