Direct links between estrogen and AD pathology have also been reported, as estradiol promotes non-amyloidogenic processing by upregulating Aβ-degradation enzymes (Merlo and Sortino, 2012), increasing secretion of amyloid precursor protein (APP), and decreasing Aβ production (Xu et al., 1998; Manthey et al., 2001; Nord et al., 2010), and via its action on insulin degrading enzyme, a protease involved in Aβ degradation (Zhao et al., 2011). The gene discussed is APP; the disease is Alzheimer disease.