Toward the Noninvasive Diagnosis of Alzheimer's Disease: Molecular Basis for the Specificity of Curcumin for Fibrillar Amyloid-ß.

ABSTRACT

Recent studies show that curcumin, a naturally fluorescent dye, can be used for the noninvasive optical imaging of retinal amyloid-ß (Aß) plaques. We investigated the molecular basis for curcumin's specificity for hierarchical Aß structures using molecular dynamics simulations, with a focus on how curcumin is able to detect and discriminate different amyloid morphologies. Curcumin inhibits and breaks up ß-sheet formation in Aß monomers. With disordered Aß structures, curcumin forms a coarse-grained composite structure. With an ordered fibril, curcumin's interaction is highly specific, and the curcumin molecules are deposited in the fibril groove. Curcumin tends to self-aggregate, which is finely balanced with its affinity for Aß. This tendency concentrates curcumin molecules at Aß deposition sites, potentially increasing the fluorescence signal. This is probably why curcumin is such an effective amyloid imaging agent.