Deficiency of the copper chaperone for superoxide dismutase increases amyloid-β production.

The copper chaperone for superoxide dismutase (CCS) binds to both the β-site AβPP cleaving enzyme (BACE1) and to the neuronal adaptor protein X11α. BACE1 initiates AβPP processing to produce the amyloid-β (Aβ) peptide deposited in the brains of Alzheimer's disease patients. X11α also interacts directly with AβPP to inhibit Aβ production. However, whether CCS affects AβPP processing and Aβ production is not known. Here we show that loss of CCS increases Aβ production in both CCS knockout neurons and CCS siRNA-treated SHSY5Y cells and that this involves increased AβPP processing at the BACE1 site.