Several potential mechanisms have been proposed: (1) estrogen may act on interlukin 6 to antagonize inflammation [193]; (2) the phenolic structure of estrogen may contribute to its antioxidant effect in cells [194]; (3) estrogen may reduce the level of appolipoprotein E (ApoE), with the isoform ApoE4 being a strong risk factor for AD development [195]; and (4) gonadal steroids may reduce the protein level of PS1 and thus γ-secretase activity [196]. Here, APOE is linked to Alzheimer disease.