Stress has been implicated as a risk factor for Alzheimer disease (AD), and altered stress signalling has been demonstrated in mouse models of AD, but the mechanisms underlying the involvement of stress in AD pathogenesis remain elusive. Cheng Zhang and colleagues treated female AD model mice with the corticotropin-releasing factor receptor 1 antagonist R121919, and found that inhibition of corticotropin signalling mitigated amyloid-β pathology and prevented onset of cognitive impairment. No signs of toxicity or tolerability issues associated with R121919 administration in mice were observed, but its safety in humans is unknown.