Specific apolipoprotein E (apoE) alleles determines, in large part, the risk and mean age of onset familial and sporadic Alzheimer disease. The unresolved issues in this relationship support the contribution of other environmental and genetic parts. Among the candidates the apolipoprotein A-IV (apoA-IV) a component of plasma lipid particles similar to apoE has been suggested to play a role in brain metabolism. Since apoA-IV has a common DNA based protein polymorphism with a different function we determined apoA-IV (360:Gln:His) DNA polymorphism in 63 late-onset sporadic Alzheimer's patients. We found that the APOA-IV (360:His) heterozygosity occurs significantly more frequent (20.6% vs. 7.0%, P = 0.021, odds ratio 3.4 (confidence interval 1.1-10.2)) comparing age-matched controls with normal mental score. The significant difference in apoA-IV allelic distribution has been detected dominantly in patients with non-apoE4 genotype. Our data indicate that the apoA-IV-2 allele may confer one of the susceptibility markers for Alzheimer's disease (AD) and strengthen the polygenic risk determination of the variability in expression of AD.