Effects of NSAIDs on Aβ42 in Tg2576 brain. The graphs illustrate the percent of control values seen in each experimental group ± SEM, and the number in parentheses indicates mice per group. Treated groups were compared with controls using ANOVA with Dunnet’s post hoc correction. (a) Survey of FDA-approved NSAIDs. Brain levels of Aβ were determined after 3 days of oral dosing and compared with controls treated with vehicle alone. All animals were treated with 50 mg/kg per day except for indomethacin, which was dosed at 10 mg/kg per day (^#P = 0.051, *P < 0.03, **P < 0.01). A statistically significant 17% reduction in Aβ42 levels is seen in the diclofenac treatment group (n = 8 animals), whereas a nonsignificant trend is noted in the piroxicam treatment group (n = 4), despite the fact that the average decrease in Aβ42 levels is larger (19%). Control values for the untreated Tg2576 mice are 18.5 ± 0.7 pM/gm for Aβ40 and 7.7 ± 0.3 pM/gm for Aβ42. (b) Dose-response studies with R- and S-flurbiprofen. Brain levels of Aβ were determined after 3 days of oral dosing and compared with controls treated with vehicle alone. All of these treatments significantly lowered Aβ42 levels. Treatment with 25 and 50 mg/kg per day of S-flurbiprofen also lowered Aβ40 levels, an effect possibly attributable to toxicity; no effect was seen on Aβ40 with R-flurbiprofen treatment (*P < 0.01, **P < 0.01). (c) Comparison between Aβ42 levels in cell culture and in transgenic mice. Mean inhibition of Aβ42 production is shown in the H4 cell line (in vitro, gray bars) and in TG2576 mice (in vivo, black bars).