Synthesis and biological evaluation of curcumin analogs as β-amyloid imaging agents.

Aim: Detection of β-amyloid (Aβ) plaques in the brain is a very promising biomarker approach for early diagnosis of Alzheimer's disease (AD).

Materials & Methods: A series of curcumin analogs (1,5-diphenyl-1,4-pentadien-3-one derivatives) were synthesized and evaluated. Specific binding to Aβ plaques was demonstrated in vitro using postmortem AD homogenates, and the fluorescent staining and autoradiography in vitro of postmortem AD brain sections were performed.

Results: Some compounds showed high binding affinities with Aβ plaques. Fluorescent staining indicated that compound 4e clearly stained Aβ plaques within AD brain sections. In biodistribution, radioiodinated ligand [I]4e exhibited high brain uptake and favorable clearance from the brain. Autoradiography in vitro further confirmed the high affinities of [I]4e.

Conclusion: The results strongly suggested that [I]4e might be developed into potential amyloid imaging agent for the detection of senile plaques in AD. [Formula: see text].