Redox behaviour of Cu-Aβ(4-16) complexes related to Alzheimer's Disease

The development of Alzheimer’s Disease (AD) has been linked to abnormal quantities of β-amyloid peptides in the brain. The majority of studies have focussed on Aβ(1-40/42) amyloids and their Cu(II)-Aβ(1-40/42) complexes which are responsible for production of reactive oxygen and nitrogen species (ROS and RNS), which are highly toxic to neurons. According to recent studies on amyloid plaques, Aβ(4-42), which is an N-truncated version of Aβ(1-42), is as prevalent as Aβ(1-42) in the brain. Although Cu(II) ions, bounded by Aβ(4-42), can be oxidized to highly reactive Cu(III) ions, its Cu(II) complexes do not appear to contribute to ROS/RNS formation. In this paper, the pH-dependent voltammetric response of Aβ(4-16)-Cu(II) complexes is investigated to understand the influence of the deprotonation of tyrosine within the complex towards the Cu(II)/Cu(III) reaction. The results will help to better understand the scavenging role of tyrosine in quenching highly reactive Cu(III) ions not only in Aβ(4-x)-Cu(II) complexes but also provide clues to the reactive properties of other tyrosine-containing amyloid-metal complexes.