The hemochromatosis gene affects the age of onset of sporadic Alzheimer's disease

NEUROBIOL AGING. In the present study we analysed the genotype of HFE, the gene involved in hemochromatosis, in 107 patients with sporadic late-onset AD and in 99 age-matched non-demented controls. We observed that patients c arrying the mutant HFE-H63D allele had a mean age at onset of 71.7 +/- 6.0 years versus 76.6 +/- 5.8 years of those who were homozygous for the wild-t ype allele (p = 0.001). The frequency of the HFE-H63D mutation was highest (0.22) in the patients aged < 70 years at the time of disease onset, wherea s it was 0.12 in those with disease onset at an age of 70-80 years, and 0.0 4 in those aged more than 80 years, The APOE genotype did not significantly modify the effect of HFE on age at onset. We conclude that mild disturbanc es of iron homeostasis associated with a common genetic determinant may int eract with other pathogenic mechanisms involved in AD. HFE mutations may an ticipate AD clinical presentation in susceptible individuals. (C) 2001 Else vier Science Inc. All rights reserved.