It is likely that amyloid beta-protein (A beta) mediates nerve cell death in Alzheimer's disease (AD). Some nerve cell populations, however, remain undamaged in AD brain. To understand the biochemical basis for resistance to A beta toxicity, a series of cell lines were isolated which are resistant to A beta toxicity. It is shown that a major component of the resistance mechanism is the transcriptional elevation of two H2O2 degrading enzymes, glutathione peroxidase and catalase. These data support other evidence for the role of oxidative damage in A beta toxicity, and suggest strategies for clinical approaches to the disease.