Ibuprofen reduces Aβ, hyperphosphorylated tau and memory deficits in Alzheimer mice

We examined the effects of ibuprofen on cognitive deficits, A beta and tau accumulation in young triple transgenic (3xTg-AD) mice. 3xTg-AD mice were fed ibuprofen-supplemented chow between 1 and 6 months. Untreated 3xTg-AD mice showed significant impairment in the ability to learn the Morris water maze (MWM) task compared to age-matched wild-type (WT) mice. The performance of 3xTg-AD mice was significantly improved with ibuprofen treatment compared to untreated 3xTg-AD mice. Ibuprofen-treated transgenic mice showed a significant decrease in intraneuronal oligomeric A beta and hyperphosphorylated tau (AT8) immunoreactivity in the hippocampus. Confocal microscopy demonstrated co-localization of conformationally altered (MC1) and early phosphorylated tau (CP-13) with oligomeric A beta, and less co-localization of oligomeric A beta and later forms of phosphorylated tau (AT8 and PHF-1) in untreated 3xTg-AD mice. our findings show that prophylactic treatment of young 3xTg-AD mice with ibuprofen reduces intraneuronal oligomeric A beta, reduces cognitive deficits, and prevents hyperphosphorylated tau immunoreactivity. These findings provide further support for intraneuronal A beta as a cause of cognitive impairment, and suggest that pathological alterations of tau are associated with intraneuronal oligomeric A beta accumulation. (C) 2008 Elsevier B.V. All rights reserved.