Figure 5.

Model for mechanism of action of metal ion-modulated Aβ self-assembly. (a) Transition-metal ions, in particular referring to Cu(II), Zn(II), and Ag(I) ions, specifically prevent fibril-end elongation events by forming a seemingly aggregation-inert metal-bound Aβ complex. Inhibition of fibril elongation predicts an enhanced rate of oligomer generation. At high metal ion concentration, other aggregation processes dominate, and amorphous aggregates are formed. (b) An energy diagram shows the concentration-dependent formation of Aβ fibrils and amorphous Aβ aggregates, where an increased concentration of Aβ generally enhances aggregation and the energy barrier toward amorphous aggregate formation is determined by the metal ion concentration. The figure was modified with permission from ref (1). Copyright 2022 the authors. American Chemical Society.