The Apolipoprotein E (APOE) epsilon 4 allele has been found to be strongly associated with Alzheimer's disease (AD) in most studies conducted up to now, though not all investigators have established a similar association with other forms of dementia, like vascular dementia. Our study examined the APOE polymorphism in a sample of 149 dementia patients, of which there were 80 with probable sporadic late-onset AD, 16 with a mixed form of dementia (MD), and 53 with vascular dementia (VD). An elderly control sample was composed of 126 subjects. The data obtained on the whole AD sample did not confirm the association already reported with APOE epsilon 4. A difference did emerge when the subjects were subdivided on the basis of age at the examination. AD patients aged < or = 80 years significantly differed from the correspondent elderly controls, while no difference was observed between the patients aged 81 years or older and controls. This pattern could be due to a previous disadvantageous effect of the epsilon 4 allele on the subjects bearing it. A substantially similar pattern was observed in the few MD patients, while no differences were found in the two VD subgroups. The odds ratio (OR) for AD associated with at least one epsilon 4 allele was significant and equal to 3.3 (95% CI = 1.2-9.1) for the < or = 80 age class, while it was not significant and equal to 1.1 (95% CI = 0.4-2.8) for the > 80 age class. Our data indicate that in AD patients aged less than 81 years, epsilon 4 is clearly associated with AD and that it can be considered a risk factor for AD chiefly before this age.