Interactions of Zn(II) and Cu(II) ions with Alzheimer's amyloid-beta peptide. Metal ion binding, contribution to fibrillization and toxicity.

ABSTRACT

Amyloid-ß peptides (Aß) are key molecules in Alzheimer's disease (AD) pathology as they form amyloid plaques that are primary hallmarks of AD. There is increasing evidence demonstrating that the biometals zinc(ii) and copper(ii) interact with Aß peptides and have an influence on their fibrillization and toxicity. Zinc and copper ions are abundantly present in the synaptic areas of the brain, and it is likely that the age-related dyshomeostasis of these biometals is associated with AD pathology. In this review we summarize the knowledge of the interactions of zinc and copper ions with Aß peptides, their role in Aß fibrillization and toxicity and provide a critical analysis of the conflicting results in the field. Copper ions entrapped in Aß fibrils are electrochemically active and can generate ROS in the presence of hydrogen peroxide and reducing agents. This might provide a key for understanding the putative role of copper in Aß toxicity and AD pathology.