Curcumin derivative with the substitution at C-4 position, but not curcumin, is effective against amyloid pathology in APP/PS1 mice

Recent evidence supports the amyloid cascade hypothesis that a pathological change of amyloid beta (A beta) in the brain is an initiating event in Alzheimer's disease (AD). Accordingly, modulating the abnormal A beta aggregation is considered a potential therapeutic target in AD. Curcumin, a low-molecular-weight polyphenol derived from the well-known curry spice turmeric, has shown favorable effects on preventing or treating AD pathology. The present study investigated the effects of curcumin and 2 novel curcumin derivatives, FMeC1 and FMeC2, on AD pathology in APPswe/PS1dE9 double transgenic mice. Mice fed a chow diet that contained FMeC1 for 6 months showed a reduction in insoluble A beta deposits and glial cell activity together with reduced cognitive deficits, compared to animals receiving a control diet or with curcumin or FMeC2 in their diet. Both curcumin and FMeC1 modulated the formation of A beta aggregates; however, only FMeC1 significantly attenuated the cell toxicity of A beta. These results indicate that FMeC1 may have potential for preventing AD. (C) 2015 Elsevier Inc. All rights reserved.