Molecular interactions, structural effects, and binding affinities between silver ions (Ag+) and amyloid beta (Aβ) peptides

Because silver is toxic to microbes, but not considered toxic to humans, the metal has been used as an antimicrobial agent since ancient times. Today, silver nanoparticles and colloidal silver are used for antibacterial purposes, and silver-peptide and similar complexes are being developed as therapeutic agents. Yet, the health effects of silver exposure are not fully understood, nor are the molecular details of silver-protein interactions. In Alzheimer's disease, the most common form of dementia worldwide, amyloid-β (Aβ) peptides aggregate to form soluble oligomers that are neurotoxic. Here, we report that monovalent silver ions (Ag⁺) bind wildtype Aβ₄₀ peptides with a binding affinity of 25 ± 12 µM in MES buffer at 20 °C. Similar binding affinities are observed for wt Aβ₄₀ peptides bound to SDS micelles, for an Aβ₄₀(H6A) mutant, and for a truncated Aβ(4-40) variant containing an ATCUN (Amino Terminal Cu and Ni) motif. Weaker Ag⁺ binding is observed for the wt Aβ₄₀ peptide at acidic pH, and for an Aβ₄₀ mutant without histidines. These results are compatible with Ag⁺ ions binding to the N-terminal segment of Aβ peptides with linear bis-his coordination. Because the Ag⁺ ions do not induce any changes in the size or structure of Aβ₄₂ oligomers, we suggest that Ag⁺ ions have a minor influence on Aβ toxicity.