Objectives: The aim was to examine the gene environment (GxE) interaction with reference to APO E genotypes, serum lipids and organochlorine pesticides (OCPs) as one of the factors in the etiology of Alzheimer’s disease (AD). Methods: A case control study was used to examine, APOE HhaI polymorphism by polymerase chain reaction (PCR)/PCR–restriction fragment length polymorphism method, serum lipids by autoanalyser and OCPs by gas chromatography (GC). Results: APOE 4 allele frequency was significantly high (p=0.000, OR=5.73, CI=2.68-12.50) in AD as compared to controls. The serum cholesterol, β- hexachlorocyclohexane and dieldrin are risk factors for AD independent of the APOE 4 risk allele, recording an odds ratio of 1.16, 11.38 and 10.45 respectively. Conclusion: GxE interactions exist with APOE 4 allele status that need to be considered for the study design and analysis of such data in future studies of AD.