APP and Alzheimer disease: Contrary to female AD mice, removal of male gonadal steroids significantly reduced the expression of endogenous App, again without a change in macroH2A1 binding at App. Our data suggest that female steroid hormones reduce endogenous App and tau expression (the latter by targeting macroH2A1 as a crucial regulator of the tau gene), whereas male steroid hormones play an opposing role by increasing endogenous App, independent of macroH2A1 regulation.