Bivalent ligand containing curcumin and cholesterol as a fluorescence probe for Aβ plaques in Alzheimer's disease

A recently developed bivalent ligand BMAOI 14 (7) has been evaluated for its ability to label and detect aggregated β-amyloid (Aβ) peptide as a fluorescent probe. This probe contains curcumin as the Aβ recognition moiety and cholesterol as an anchor to the neuronal cell membrane-lipid rafts. The results demonstrate that 7 binds to the monomers, oligomers, and fibrils of Aβ42 with low micromolar to submicromolar binding affinities. This chemical probe also has many of the required optical properties for use in imaging and can rapidly cross the blood-brain barrier in vivo. Furthermore, 7 specifically binds to Aβ plaques in both Alzheimer's disease human patients and Aβ precursor protein transgenic mouse brain tissues. Collectively, these results suggest that 7 is a strong candidate as an Aβ imaging agent and encourage further optimization of 7 as a new lead for the development of the next generation of Aβ imaging probes.