The effect of Aβ conformation on the metal affinity and aggregation mechanism studied by circular dichroism spectroscopy

The conformational change and associated aggregation of beta amyloid (A beta) with or without metals is the main cause of Alzheimers'disease (AD). In order to further understand the effects of A beta and its associated metals on the aggregation mechanism, the influence of A beta conformation on the metal affinity and aggregation was investigated using circular dichroism (CD) spectroscopy. The A beta conformation is dependent on pH and trifluoroethanol (TFE). The binding of metals to A beta was found to be dependent on the A beta conformation. The aggregation induced by A beta itself or its associated metals is completely diminished for A beta in 40% TFE. Only in 5% and 25% TFE can A beta undergo an alpha-helix to beta-sheet aggregation, which involve a three-state mechanism for the metal-free state, and a two-state transition for the metal-bound state, respectively. The aggregation-inducing activity of metals is in the order, Cu2+ > Fe3+ >= Al3+ > Zn2+.