Curcuminoid Binds to Amyloid-β1-42 Oligomer and Fibril

Studies of Alzheimer's disease (AD) strongly support the hypothesis that amyloid-beta (A beta) deposition in the brain is the initiating event in the progression of AD. A beta peptides easily form long insoluble amyloid fibrils, which accumulate in deposits known as senile plaques. On the other hand, recent work indicated that soluble A beta oligomers, rather than monomers or insoluble A beta fibrils, might be responsible for neuronal and synaptic dysfunction in AD. Curcumin, a low molecular weight yellow-orange pigment derived from the turmeric plant, has shown therapeutic effects in transgenic mouse models of AD. However, it remains unclear whether curcumin interacts directly with the A beta oligomers. This study investigated any interaction between curcumin and A beta oligomers such as globulomer and A beta-derived diffusible ligand (ADDL). Globulomer was observed as a cluster of spherical structures by electron microscopic analysis, and ADDL was also detected as small spherical structures. Fluorescence analysis revealed a significant increase in the fluorescence of curcumin when reacted with both oligomers. Furthermore quartz crystal microbalance analysis showed significant frequency decreases in oligomer-immobilized electrodes following the addition of curcumin. These results strongly suggested that curcumin binds to A beta oligomers and to A beta fibrils. The association of curcumin with A beta oligomers may contribute to the therapeutic effect on AD. Based on these findings, curcumin could provide the basis of a novel concept in AD therapies targeting A beta oligomers.