The apolipoprotein E (APOE) E4 allele is associated with Alzheimer's disease, 
cardiovascular disease, and decreased longevity. To probe the mechanism of these 
associations, cell lines were created which secrete each apoE isoform. ApoE 
conditioned media, purified apoE, and commercially obtained apoE protected B12 
cells from hydrogen peroxide cytotoxicity with E2 > E3 > E4. Physiological 
levels of apoE protected cells from beta-amyloid peptides, while higher doses of 
apoE led to increased cytotoxicity. E2 > E3 > E4 possessed antioxidant activity, 
and apoE bound certain metal ions. The decreased antioxidant activity of E4 
could contribute to its association with Alzheimer's disease, cardiovascular 
disease and decreased longevity.