MAPT and Alzheimer disease: For instance, vitamin A and its metabolite, retinoic acid, have been shown to modulate the effects of estrogen signaling by increasing aromatase and ERβ expression in rat hippocampal cultured slices [71] and by reducing tau hyperphosphorylation and amyloid toxic fragments in the hippocampus of male 3×Tg-AD mice, a widely used AD mouse model.