Kinetics Of The Interconversion Between Two Physiologically Important Copper-Bound Amyloid-Beta Species

To better understand the physiological behaviour of Aβ in the brain, the kinetics of the interactions between metal ions and Aβ is crucial. In 1:1 stoichiometry binding between cooper ions and Aβ, two major conformations have been characterized in equilibrium in literature. We found that Aβ binds to a first copper ion with a near diffusion limited rate constant ∼10 ∧ 8 M ∧ {-1}s ∧ {-1}, to a second copper ion at a rate constant ∼10 ∧ 5 M ∧ {-1}s ∧ {-1}, and further copper ions. The reaction between EDTA and a mixture of 50 nM Aβ and various amounts of copper ions ranging from nM to 10 μM shows the evolution of multiple copper-Aβ species as a function of copper concentration. Most interestingly, the ratio of the two major species at low copper concentrations depends on EDTA concentration, suggesting the interconversion between them, with the rates in the order of s ∧ {-1}. Whether this interconversion is relevant to the roles of Aβ in health and disease is unclear.