Recently several reports have extended the apolipoprotein E (APOE) epsilon 4 association found in late-onset Alzheimer's disease (LOAD) patients to early-onset (EO) AD patients. We have studied this question in a large population of 119 EOAD patients (onset < or = 60 years) in which family history was carefully assessed and in 109 controls. We show that the APOE epsilon 4 allele frequency is increased only in the subset of patients who belong to families where LOAD secondary cases are present. Our sampling scheme permits us to demonstrate that for an individual, bearing at least one epsilon 4 allele increases both the risk of AD before age 60 and the probability of belonging to a family with late-onset affected subjects. Our results suggest that a subset of EOAD cases shares a common determinism with LOAD cases.