The H63D mutation in the hemochromatosis gene (HFE) has recently been considered as a risk factor in Alzheimer`s disease (AD) with advancing age at onset of the disease, independently of the apolipoprotein E (ApoE) Ε4 allele effect. We examined the distribution of the H63D mutation and ApoE genotypes as a function of age at AD onset in 328 patients with sporadic AD. Our data show that the mutant H63D allele potentially interacts with the ApoE Ε4 allele to significantly reduce age at onset of AD compared to ApoE Ε4 carriers alone, but has no effect on age at onset in ApoE Ε4 non-carriers.