Introduction of a Fluorescent Probe to Amyloid-β to Reveal Kinetic Insights into Its Interactions with Copper(II)

The kinetics of the interactions between amyloid- (A) and metal ions are crucial to understanding the physiological and pathological roles of A in the normal brain and in Alzheimer's disease. Using the quenching of a fluorescent probe by Cu2+, the mechanism of A/Cu2+ interactions in physiologically relevant conditions has been elucidated. Cu2+ binds to A at a near diffusion-limited rate, initially forming componentI. The switching between componentI and II occurs on the second timescale, with a significant energy barrier. ComponentI is much more reactive towards Cu2+ ligands and likely responsible for initial A dimer formation. Clioquinol (CQ) is shown to sequester Cu2+ more effectively than other tested ligands. These findings have implications for the potential roles of A in regulating neurotransmission, and for the screening of small molecules targeting A-metal interactions.