Redox Behavior of β-Amyloid-Cu2+ Complexes Involved in Alzheimer’s Disease

Alzheimer's disease (AD) is the most common cause of dementia in the world, affecting more than 30 millions elders. The hallmark of AD is a progressive loss of cholinergic neurons with deterioration of memory and cognition, associated to the abnormal extracellular deposition of β-amyloid (Aβ) aggregates, and high concentrations of transition metal ions such as Cu, Fe and Zn in the brain. Aβ displays a high binding affinity for Cu 2+ . In addition, Aβ-metal complexes have been proposed to participate in the generation of reactive oxygen species (ROS), which in turn cause neuronal damage [1]. The coordination properties of Cu 2+ binding sites in Aβ have been extensively studied, as reviewed in [2]. This study focuses in the electrochemical characterization of the different Aβ-Cu 2+ complexes that are formed, as a function of pH and relative Cu:protein concentrations. Cu 2+ coordination to different variants of the Aβ(1-16) fragment were characterized by spectroscopic techniques such as electron paramagnetic resonance, electronic absorption and circular dichroism in the UV-Vis region. The redox properties of these Aβ-Cu complexes were evaluated using cyclic voltammetry, revealing that different Cu 2+ coordination modes display different redox behaviors. These results add to the few electrochemical studies reported for Aβ-Cu 2+ complexes [37], and they give further insight into the redox relevance of Aβ-Cu 2+ interactions.