BACKGROUND The ε4 allele of Apolipoprotein E is involved in lipid metabolism. Oxidative stress produces an increase in lipid peroxidation that has been implicated in the pathogenic cascade in Alzheimer's disease. This study estimated the effect of the ε4 allele, malondialdehyde and lipid levels on the risk for Alzheimer's disease. METHODS A total of 41 control subjects and 73 patients with Alzheimer's disease were recruited. The Apolipoprotein E genotype was determined by amplification of exon 4 of the Apolipoprotein E by polymerase chain reaction (PCR); malondialdehyde concentration was determined by high-pressure liquid chromatography, and serum lipids were measured by routine photometric techniques. RESULTS Malondialdehyde levels were significantly higher in Alzheimer's disease patients independent of the Apolipoprotein E genotype and ε4 allele. The ε4 allele increases the risk of Alzheimer's disease by 5.114 times and elevated malondialdehyde levels increase the risk by 9.342. CONCLUSION The presence of ε4 allele and elevated malondialdehyde levels are independent risk factors for Alzheimer's disease. These findings support the hypothesis that lipid peroxidation and ε4 allele contribute to the pathogenic cascade in Alzheimer's disease by different pathways.