P3‐346: Curcumin decreases tau pathology and mortality in transgenic mouse models of Alzheimer's disease

Several transgenic mice models mimic the pathological changes of Alzheimer's disease (AD). Amongst these, JNPL3 mice overexpress P301L tau and develop neurofibrillary tangles (NFT) and motor deficits, and Tg2576 mice overexpress APPsw and develop amyloid plaques. JNPL3xTg2576 mice have both plaques and NFT. APP and tau may interact in contributing to AD. Curcumin is a multi-potent compound with anti-oxidative, anti-inflammatory, anti-Aβ aggregating, metal-chelating and JNK activity-suppressing effects. Thus, we sought to determine whether curcumin can reduce the level of NFT in brain and improve the motor function of JNPL3 mice, and magnify protective effects in JNPL3xTg2576 mice by targeting multiple pathways in AD. Eight-month-old homozygous JNPL3 and hemizygous Tg2576, and five- and eleven-month-old JNPL3xTg2576 mice were fed chow containing 500 ppm or no curcumin for five or six months before being killed. Brains of JNPL3 were fixed for Bielschowsky's staining. NFT were counted in pons sections. Sixteen-month-old JNPL3 male mice were fed peanut butter (1 μL/g body weight) with or without 100 ppm (w/v) curcumin five times per week for ten weeks. Motor function was monitored by rotarod test. Mortality difference was compared by Fisher's exact test. The number of NFT was 25% less in JNPL3 mice fed chow with than without curcumin (p = 0.034). Motor function did not significantly differ in mice fed peanut butter with than without curcumin, perhaps due to the advanced age of the mice and the short treatment duration. Mortality was significantly reduced by curcumin in all mice (p = 0.05), and in all males (p = 0.009) but not females. Amongst strains, the most significant mortality reduction occurred in JNPL3xTg2576 males (p = 0.012). Curcumin significantly decreased NFT and mortality, suggesting multiple functions of curcumin and enhanced protection in the presence of both amyloid and NFT pathologies. Therefore, curcumin could be used as a potential candidate for the treatment of AD.