Pharmacological activation of brain Retinoid X Receptors (RXRs) enhances cognition and facilitates amyloid-beta (Aβ) clearance in Alzheimer's disease (AD) mouse models, partly by upregulating apolipoprotein E (<i>Apoe</i>), a major AD genetic risk factor. This evidence concerns the gene APOE and early-onset autosomal dominant Alzheimer disease.