The curry spice curcumin reduces oxidative damage and amyloid pathology inan Alzheimer transgenic mouse

Inflammation in Alzheimer's disease (AD) patients is characterized by incre ased cytokines and activated microglia. Epidemiological studies suggest red uced AD risk associates with long-term use of nonsteroidal anti-inflammator y drugs (NSAIDs). Whereas chronic ibuprofen suppressed inflammation and pla que-related pathology in an Alzheimer transgenic APPSw mouse model (Tg2576) , excessive use of NSAIDs targeting cyclooxygenase I can cause gastrointest inal, liver, and renal toxicity. One alternative NSAID is curcumin, derived from the curry spice turmeric. Curcumin has an extensive history as a food additive and herbal medicine in India and is also a potent polyphenolic an tioxidant. To evaluate whether it could affect Alzheimer-like pathology in the APPSw mice, we tested a low (160 ppm) and a high dose of dietary curcum in (5000 ppm) on inflammation, oxidative damage, and plaque pathology. Low and high doses of curcumin significantly lowered oxidized proteins and inte rleukin-1 beta, a proinflammatory cytokine elevated in the brains of these mice. With low-dose but not high-dose curcumin treatment, the astrocytic ma rker GFAP was reduced, and insoluble beta -amyloid (A beta), soluble A beta , and plaque burden were significantly decreased by 43-50%. However, levels of amyloid precursor (APP) in the membrane fraction were not reduced. Micr ogliosis was also suppressed in neuronal layers but not adjacent to plaques . In view of its efficacy and apparent low toxicity, this Indian spice comp onent shows promise for the prevention of Alzheimer's disease.