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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 carrying 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-type 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, whereas it was 0.12 in those with disease onset at an age of 70-80 years, and 0.04 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 disturbances of iron homeostasis associated with a common genetic determinant may interact with other pathogenic mechanisms involved in AD. HFE mutations may anticipate AD clinical presentation in susceptible individuals.

Type

Journal article

Journal

Neurobiol Aging

Publication Date

07/2001

Volume

22

Pages

563 - 568

Keywords

Age of Onset, Aged, Aged, 80 and over, Alzheimer Disease, Apolipoprotein E4, Apolipoproteins E, Female, Gene Frequency, Genotype, HLA Antigens, Hemochromatosis, Hemochromatosis Protein, Histocompatibility Antigens Class I, Humans, Male, Membrane Proteins, Middle Aged, Mutation, Risk Factors