HFE variants, APOE and Alzheimer's disease: Findings from the population-based Rotterdam Study
Iron is a reactive oxygen species and has been implicated in the pathogenesis of Alzheimer's disease (AD). In a population-based cohort study, including 268 incident AD patients and 2079 control individuals, we investigated the influence of the HFE C282Y and H63D variants and the apolipoprotein E4 (APOEε4) allele on the incidence, and age at onset of AD. There was no significant difference in the frequency of HFE variants in AD patients compared to controls. There was no significant effect modification by the APOEε4 allele. The mean age at onset was earlier in H63D homozygotes compared to non-carriers of this variant, in men (76.9 ± 3.2 compared to 82.2 ± 1.7) and women (82.1 ± 3.9 compared to 84.5 ± 1.7). In addition, in APOEε4 carriers, the mean age at onset of AD was earlier in men homozygous for the H63D variant (73.2 ± 2.1 versus 78.7 ± 1.6, p = 0.05). Our results suggest that HFE variants are not strong determinants of AD in the general population but may modify the age of onset.