The behavioural deficits and neurodegeneration that are observed in late-onset Alzheimer's disease are linked to high levels of amyloid-β (Aβ) in the brain, which result from a failure of Aβ clearance mechanisms. Here, the authors treated mice exhibiting Aβ-associated behavioural deficits and pathology with the retinoid X receptor (RXR) agonist bexarotene. RXR activation induces the expression of apolipoprotein E, which facilitates Aβ removal from the brain. Bexarotene treatment rapidly lowered soluble and insoluble levels of brain Aβ and improved cognitive, behavioural and olfactory deficits, indicating that RXR agonists may be useful in the treatment of Alzheimer's disease.