The Alzheimer's disease amyloid precursor protein modulates copper- induced toxicity and oxidative stress in primary neuronal cultures

Abstract

The amyloid precursor protein (APP) of Alzheimer's disease can reduce copper (II) to copper (I) in a cell-free system potentially leading to increased oxidative stress in neurons. We used neuronal cultures derived from APP knock-out (APP(-/-)) and wild-type (WT) mice to examine the role of APP in copper neurotoxicity. WT cortical, cerebellar, and hippocampal neurons were significantly more susceptible than their respective APP(-/-)) neurons to toxicity induced by physiological concentrations of copper but not by zinc or iron. There was no difference in copper toxicity between APLP2(-/-)) and WT neurons, demonstrating specificity for APP-associated copper toxicity. Copper uptake was the same ..