APP23 OVX mice contain estrogen in the brain.Only APP/Ar(+/-) but not APP23 OVX mice had reduced Aβ plaques following E2 or genistein (G) treatment.E2 and G treatment to APP/Ar(+/-) resulted decreased BACE1 mRNA and protein expression.E2 or genistein supplementation might reduce AD neuropathological changes by increased neuroE2 concentrations. The gene discussed is APP; the disease is Alzheimer disease.