To study effect of ERβ activation on AD pathology we treated AppNL-G-F male and female mice with the selective ERβ agonist LY500307 (with 12-fold higher selectivity for ERβ over ERα and 32-fold more functional potency (19, 20)), 0.35 mg/kg daily through oral gavage every other week over 5 weeks, starting at 3 months of age. This evidence concerns the gene ESR2 and Alzheimer disease.