This study investigated effects of NSAID ibuprofen and dietary curcumin on Aβ neuropathology and cognitive deficits in aged Sprague-Dawley rats given an intracerebroventricular infusion of Abeta peptides. Oxidative damage has been hypothesized to play a central role in AD pathogenesis. Although CNS inflammation may contribute to oxidation, aspects of inflammation unrelated to oxidation, such as complement activation, are likely to contribute to AD pathogenesis. Therefore intervention strategies for AD may require targeting both oxidation and inflammation. Curcumin is both a potent antioxidant and an effective antiinflammatory agent. In this study, dietary curcumin (2000 ppm), but not ibuprofen, suppressed oxidative damage (isoprostane levels) and synaptophysin loss. Both ibuprofen and curcumin reduced microgliosis in cortical layers, but curcumin increased microglial labeling within and adjacent to Aβ -ir deposits. In a second group of middle-aged female SD rats, 500 ppm dietary curcumin prevented Aβ -infusion induced spatial memory deficits in the Morris Water Maze and post-synaptic density (PSD)-95 loss and reduced Aβ deposits. Because of its low side-effect profile and long history of safe use, curcumin may find clinical application for AD prevention.