The data demonstrate that the HFEH63D polymorphism reduces apparent brain integrity in AD carriers. AD-HFEH63D carriers have reduced white matter integrity, increased cortical loss, increased amyloid-beta (Aβ) deposition, and an accelerated disease course trajectory compared to HFEWT carriers in regions susceptible to AD pathology. This work helps decipher how HFE mutations affect AD trajectory, regional susceptibility to AD pathology, brain aging integrity, and cognitive decline.
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