Copper enhances APP dimerization and promotes Aβ production

Alzheimer's disease (AD) is characterized by the deposition of amyloid-beta (A beta) plaques, senile plaque. The A beta peptide is cleaved from amyloid precursor protein (APP) by beta-secretase and gamma-secretase. Until now, many literatures have documented that the high concentration of copper is present in A beta plaques and enhances aggregation of. The APP copper binding domain (CuBD) is located in the N-terminal next to the growth factor-like domain that gets involved in APP homodimerization. Importantly, dimerization of APP has profound effect on A beta production. We investigated whether copper alters the state of APP dimerization and how it affects APP metabolism. Here, we demonstrate that copper enhanced APP dimerization and increased extracellular release of A beta. Moreover, copper chelator, D-penicillamine, suppressed APP dimerization and decreased extracellular release of A beta. These results suggest that the action of copper may be profoundly associated with the pathway of A beta production in AD pathogenesis. (c) 2013 Elsevier Ireland Ltd. All rights reserved.