The epsilon4 allele of apolipoprotein E is a risk factor for Alzheimer's disease. However, other yet unidentified factors might be involved. It has been suggested that the epsilon4 allele might be relatively less relevant in Alzheimer's disease with onset before age 60 and after age 80. The aim was to evaluate the association of the epsilon4 allele with Alzheimer's disease across a wide range of ages at onset. 156 patients with age at onset between 46 and 89 and 120 cognitively unimpaired subjects aged 53 to 89 as controls were studied. Age at onset in the cases and age in the controls were stratified into six groups (60 and younger, 60 to 64, 65 to 69, 70 to 74, 75 to 79, and 80 and older). Multivariable sex adjusted probit regression analysis was used to model epsilon4 prevalences in cases and controls across age. The sex adjusted relation of epsilon4 with age in controls was slightly negative with prevalence of 0.16 in the youngest and 0.09 in the oldest age groups. The sex adjusted relation in cases with Alzheimer's disease had a bell shaped curve with prevalence of 0.23 in the youngest age group, rising to 0.54 and 0.51 in the age groups 65 to 69 and 70 to 74, and decreasing to 0.12 in the oldest age group. It is concluded that the relation of the epsilon4 allele with Alzheimer's disease is age dependent, indicating that other risk factors might be relevant in the younger and older ages.