Keto Form Of Curcumin Derivatives Strongly Binds To A Beta Oligomers But Not Fibrils

The accumulation of beta-amyloid (A beta) aggregates in the brain occurs early in the progression of Alzheimer's disease (AD), and non-fibrillar soluble A beta oligomers are particularly neurotoxic. During binding to A beta fibrils, curcumin, which can exist in an equilibrium state between its keto and enol tautomers, exists predominantly in the enol form, and binding activity of the keto form to A beta fibrils is much weaker. Here we described the strong binding activity the keto form of curcumin derivative Shiga-Y51 shows for A beta oligomers and its scant affinity for A beta fibrils. Furthermore, with imaging mass spectrometry we revealed the blood-brain barrier permeability of Shiga-Y51 and its accumulation in the cerebral cortex and the hippocampus, where A beta oligomers were mainly localized, in a mouse model of AD. The keto form of curcumin derivatives like Shiga-Y51 could be promising seed compounds to develop imaging probes and therapeutic agents targeting A beta oligomers in the brain.