Ibuprofen effects on Alzheimer pathology and open field activity in APPsw transgenic mice

We previously showed the non-steroidal anti-inflammatory drug (NSAID) ibuprofen suppresses inflammation and amyloid in the APPsw (Tg2576) Tg2576 transgenic mouse. The mechanism for these effects and the impact on behavior are unknown. We now show ibuprofen's effects were not mediated by alterations in amyloid precursor protein (APP) expression or oxidative damage (carbonyls). Six months ibuprofen treatment in Tg+ females caused a decrease in open field behavior (p < 0.05), restoring values similar to Tg- mice. Reduced caspase activation per plaque provided further evidence for a neuroprotective action of ibuprofen. The impact of a shorter 3 month duration ibuprofen trial, beginning at a later age (from 14 to 17 months), was also investigated. Repeated measures ANOVA of A<beta> levels (soluble and insoluble) demonstrated a significant ibuprofen treatment effect (p < 0.05). Post-hoc analysis showed that ibuprofen-dependent reductions of both soluble A<beta> and A beta 42 were most marked in entorhinal cortex (p < 0.05). Although interleukin-1<beta> and insoluble A beta were more effectively reduced with longer treatment, the magnitude of the effect on soluble A beta was not dependent on treatment duration. (C) 2001 Elsevier Science Inc. All rights reserved.