Copper and zinc binding to amyloid-beta: coordination, dynamics, aggregation, reactivity and metal-ion transfer.

The metal ions copper, zinc and iron have been shown to be involved in Alzheimer's disease (AD). Cu, Zn and Fe ions are proposed to be implicated in two key steps of AD pathology: 1) aggregation of the peptide amyloid-beta (Abeta), and 2) production of reactive oxygen species (ROS) induced by Abeta. There is compelling evidence that Cu and Zn bind directly to Abeta in AD. This formation of Cu/Zn-Abeta complexes is thought to be aberrant as they have been detected only in AD, but not under healthy conditions. In this context, the understanding of how these metal ions interact with Abeta, their influence on structure and oligomerization become an important issue for AD. Moreover, the mechanism of ROS production by Cu-Abeta in relation to its aggregations state, as well as the metal-transfer reaction from and to Abeta are crucial in order to understand why Abeta oligomers are highly toxic and why Abeta seems to bind Cu and Zn only in AD.