Oxidative stress is one of the major pathological features of Alzheimer's disease (AD). Here, we investigated whether dietary vitamin E (VE) depletion may induce adverse effects and supplementation with alpha-tocopherol (alphaT) may result in beneficial effects on redox status and the regulation of genes relevant in the pathogenesis of AD in healthy rats. Three groups of eight male rats each were fed diets with deficient ( < 1 mg alphaT equivalents/kg diet), marginal (9 mg alphaT equivalents/kg diet) or sufficient (18 mg alphaT equivalents/kg diet) concentrations of natural-source VE for 6 months; a fourth group was fed the VE-sufficient diet fortified with alphaT (total VE, 146 mg alphaT equivalents/kg diet). Feeding of the experimental diets dose dependently altered alphaT concentrations in the cortex and plasma. No significant changes in F2-isoprostane concentrations, activities of antioxidative enzymes (total superoxide dismutase, Se-dependent glutathione peroxidase) and concentrations of glutathione or the expression of AD-relevant genes were observed. In this non-AD model, depletion of VE did not induce adverse effects and supplementation of alphaT did not induce positive effects on the parameters related to the progression of AD.