Phenolic anti-inflammatory antioxidant reversal of Aβ-induced cognitive deficits and neuropathology

Both oxidative damage and inflammation have been implicated in age-related neurodegenerative diseases including Alzheimer's Disease (AD). The yellow curry spice, curcumin, has both antioxidant and anti-inflammatory activities which confer significant protection against neurotoxic and genotoxic agents. We used 22 month Sprague-Dawley (SD) rats to compare the effects of the conventional NSAID, ibuprofen, and curcumin for their ability to protect against amyloid beta -protein (A beta)-induced damage. Lipoprotein carrier-mediated, intracerebroventricular infusion of A beta peptides induced oxidative damage, synaptophysin loss, a microglial response and widespread A beta deposits. 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 A beta -ir deposits. In a second group of middle-aged female SD rats, 500 ppm dietary curcumin prevented A beta -infusion induced spatial memory deficits in the Morris Water Maze and post-synaptic density (PSD)-95 loss and reduced A beta deposits. Because of its low side-effect profile and long history of safe use, curcumin may find clinical application for AD prevention. (C) 2001 Elsevier Science Inc. All rights reserved.