Copper-amyloid beta complex (Cu-Aβ)

The copper-amyloid beta complex is a pathological molecular assembly formed by the coordination of copper ions (Cu2+ or Cu+) to the N-terminal region of the amyloid beta (Aβ) peptide, primarily involving histidine residues at positions 6, 13, and 14. This interaction is a central feature of Alzheimer's disease pathology, as copper binding significantly accelerates the aggregation of Aβ into neurotoxic oligomers and insoluble plaques (Fallon et al., 2014, Journal of Biological Chemistry). Beyond structural stabilization, the redox-active nature of copper allows the Cu-Aβ complex to catalyze the reduction of molecular oxygen, generating reactive oxygen species (ROS) such as hydrogen peroxide and hydroxyl radicals, which cause extensive oxidative damage to neuronal membranes and synapses (Bush, 2003, Trends in Neurosciences). Therapeutic interventions targeting this interface, known as metal-protein attenuating agents (MPAAs), aim to disrupt the Cu-Aβ interaction to reduce oxidative stress and promote the clearance of amyloid aggregates (Barnham & Bush, 2014, Chemical Society Reviews). By sequestering copper or redistributing it back into intracellular compartments, these drugs attempt to mitigate the neurodegenerative cascade associated with metal dyshomeostasis in the aging brain.

Other names

Amyloid-beta copper binding siteCu(II)-Abeta complexCopper-coordinated amyloid betaAβ-Cu interface

Metal-protein attenuation, competitive chelation of copper ions to prevent Aβ coordination, inhibition of redox-active metal-mediated ROS production, and promotion of amyloid plaque dissolution.