HFE gene mutation involves iron metabolism, which is shown to directly contribute to myelination process. White matter degeneration in bi-genetic mutation (HFEH63D and ApoE4 allele) carriers was investigated using DTI from the AD Neuroimaging Initiative (ADNI) database. Comparing to the HFEWT/ApoE4+ group, mean diffusivity and radial diffusivity of inferior longitudinal fasciculus in the HFEH63D/ApoE4+ group demonstrated less integrity damage and fewer late-myelination loss with aging reflecting a possible mechanism as HFE polymorphism protective role in partly eliminating ApoE4 being the high-risk factor for AD progressing.
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