Deficiency of the Copper Chaperone for Superoxide Dismutase Increases Amyloid-beta Production

The copper chaperone for superoxide dismutase (CCS) binds to both the beta-site A beta PP cleaving enzyme (BACE1) and to the neuronal adaptor protein X11 alpha. BACE1 initiates A beta PP processing to produce the amyloid-beta (A beta) peptide deposited in the brains of Alzheimer's disease patients. X11 alpha also interacts directly with A beta PP to inhibit A beta production. However, whether CCS affects A beta PP processing and A beta production is not known. Here we show that loss of CCS increases A beta production in both CCS knockout neurons and CCS siRNA- treated SHSY5Y cells and that this involves increased A beta PP processing at the BACE1 site.