Inflammation in Alzheimer's disease (AD) patients is characterized by increased cytokines and activated microglia. Epidemiological studies suggest reduced AD risk is associated with long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs). Whereas chronic ibuprofen suppressed inflammation and plaque-related pathology in an Alzheimer transgenic APPSw mouse model (Tg2576), excessive use of NSAIDs targeting cyclooxygenase can cause gastrointestinal, liver, and renal toxicity. One alternative NSAID is curcumin, which has an extensive history as a food additive and herbal medicine in India and is also a potent polyphenolic antioxidant. Lim et al. found that curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse model (114). To evaluate whether it could affect Alzheimer-like pathology in the APPSw mice, they tested the effect of a low (160 ppm) and a high dose of dietary curcumin (5000 ppm) on inflammation, oxidative damage, and plaque pathology. Low and high doses significantly lowered oxidized proteins and IL-1 h, a proinflammatory cytokine elevated in the brains of these mice. With low-dose, but not high-dose, curcumin treatment, the astrocytic marker glial fibrillary acidic protein was reduced, and insoluble h-amyloid (Ah), soluble Ah, and plaque burden were significantly decreased, by 43-50%. However, levels of amyloid precursor in the membrane fraction were not reduced. Microgliosis was also suppressed in neuronal layers but not adjacent to plaques. In view of its efficacy and apparent low toxicity, this Indian spice component showed promise for the prevention of Alzheimer's disease.
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