A and B, caffeine, an inhibitor of ATM, shows a neuroprotective effect against Aβ-induced neurotoxicity. A and B, primary cortical neurons were seeded at a density of 1 × 106 cells/ml in poly-d-lysine-coated 96-well plates. Three days after plating, cells were pretreated with 10 μM caffeine for 1 h, and subsequently treated for 16 h with 0, 2.5, or 5 μM Aβ1-42. Cell viability was determined using a CellTiter-Glo luminescent cell viability assay kit (A), and caspase-3/7 activity was determined using a Caspase-Glo™ 3/7 assay kit (B). C, after transfection as described in Fig 3B, cells were pretreated for 1 h with or without 10 μM caffeine, and then cells were further incubated with or without 5 μM Aβ1-42 for 16 h. Cell viability was determined using a CellTiter-Glo luminescent cell viability assay kit. All the values are presented as the mean ± SEM of three independent experiments. *p < 0.05, **p < 0.01 vs control siRNA. N.S., not significant, as determined by one-way ANOVA followed by Duncan's test.