The study investigates the therapeutic potential of bexarotene, an RXR agonist, in Alzheimer's disease (AD) mouse models. Bexarotene was found to enhance the clearance of β-amyloid (Aβ) from the brain, leading to a rapid reduction in Aβ levels and plaque formation. This effect was dependent on apolipoprotein E (apoE) expression. Treatment with bexarotene also reversed cognitive, social, and olfactory deficits, and improved neural circuit function. The mechanism involves activation of nuclear receptors PPARγ and LXR, which induce apoE expression and enhance Aβ clearance through macrophages and microglia. The findings suggest that RXR agonists may be effective in treating AD and its early stages.The study investigates the therapeutic potential of bexarotene, an RXR agonist, in Alzheimer's disease (AD) mouse models. Bexarotene was found to enhance the clearance of β-amyloid (Aβ) from the brain, leading to a rapid reduction in Aβ levels and plaque formation. This effect was dependent on apolipoprotein E (apoE) expression. Treatment with bexarotene also reversed cognitive, social, and olfactory deficits, and improved neural circuit function. The mechanism involves activation of nuclear receptors PPARγ and LXR, which induce apoE expression and enhance Aβ clearance through macrophages and microglia. The findings suggest that RXR agonists may be effective in treating AD and its early stages.