Several clinical trials in patients with Alzheimer disease (AD)have investigated the therapeutic potential of inhibition of β-secretase 1 (BACE1), a protease involved in the production of amyloid-β (Aβ). However, these trials thus far have failed to demonstrate a reduction in cognitive decline when given to patients with mild to moderate AD. Now, results from a new longitudinal study in a transgenic mouse model of AD suggest that this treatment was ineffective because it was given too late in the disease course. The team used two-photon microscopy in live mice to assess the kinetics of Aβ plaque deposition before and during BACE1 inhibitor treatment. BACE1 inhibition potently blocked new Aβ plaque formation but was less effective in slowing the growth of existing plaques, suggesting that the optimal timing for treatment is early in the disease course, before widespread Aβ plaque formation.