p38 MAPK phosphorylation increased in cultured neurons exposed to a nontoxic concentration of Aβ42. A, Effect of Aβ42 (200 nm) on p38 phosphorylation at different incubation times (n = 6 experiments for each group; *p < 0.05 vs control untreated cells). B, Effect of increasing concentrations of Aβ42 on p38 phosphorylation; 200 nm Aβ42 significantly increased phospho-p38 levels (n = 6 experiments in each group, *p < 0.001 vs control untreated). No additional increase was induced by higher concentrations Aβ42 (2 and 20 μm). C, Aβ42 (200 nm, 10 min incubation) or H2O2 (100 μm, 10 min) increased p38 phosphorylation compared with anti-RAGE IgG. Levels of p38 phosphorylation in cultures exposed to Aβ42 in the presence of anti-RAGE IgG were similar to those observed in cultures not exposed to Aβ42 and incubated with control IgG or in control cells (#p < 0.001). Anti-RAGE IgG pretreatment of neuronal cultures significantly reduced Aβ-, but not H2O2-induced increase in phospho-p38 (*p < 0.05 vs Aβ42 200 nm; n = 6 experiments for each group). Error bars indicate SEM.