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-sand detect aggregated beta-amyloid (A beta) peptide as a fluorescent probe. This probe contains curcumin as the A beta 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 A beta 42 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 A beta plaques in both Alzheimer's disease human patients and A beta precursor protein transgenic mouse brain tissues. Collectively, these results suggest that 7 is a strong candidate as an A beta imaging agent and encourage further optimization of 7 as a new lead for the development of the next generation of A beta imaging probes.