Cu(II) potentiation of alzheimer Aβ1-40 cytotoxicity and transition on its secondary structure

Mounting evidence has shown that dyshomeostasis of the redox-active biometals such as Cu and Fe can lead to oxidative stress, which plays a key role in the neuropathology of Alzheimer's disease (AD). Here we demonstrate that with the formation of Cu(II)-A(31-40 complexes, copper markedly potentiates the neurotoxicity exhibited by beta-amyloid peptide (A beta). A greater amount of hydrogen peroxide was released when Cu(II)-A(31-40 complexes was added to the xanthine oxidase/xanthine system detected by potassium iodide spectrophotometry. Copper bound to A beta 1-40 was observed by electron paramagnetic resonance (EPR) spectroscopy. Circular dichroism (CD) studies indicated that copper chelation could cause a structural transition of A beta. The addition of copper to A beta introduced an increase on beta-sheet as well as alpha-helix, which may be responsible for the aggregation of A beta. We hypothesized that A beta aggregation induced by copper may be responsible for local injury in AD. The interaction between Cu2+ and A beta also provides a possible mechanism for the enrichment of metal ions in amyloid plaques in the AD brain.