Development of small molecule probes for the beta-amyloid protein of Alzheimer's disease

Neurobiol Aging. Nov-Dec 1994;15(6):691-8. doi: 10.1016/0197-4580(94)90050-7.


This study describes the synthesis and in vitro testing of small molecule probes that may eventually prove useful as markers of amyloid deposition in living patients. The prototype agent, Chrysamine G (CG), is a derivative of Congo red. CG binds synthetic beta-amyloid well in vitro, as does a fluorinated derivative. The mechanism of binding appears to be the same as Congo red--through a bidentate attachment spanning several amyloid peptide chains. CG is much more lipophilic than Congo red and crosses the blood-brain barrier in normal mice, achieving a brain/blood ratio over 10/1. There was no acute toxicity in mice at doses 10 times those used in the distribution studies. CG appears to be a relatively high affinity probe for beta-amyloid that appears to have low toxicity and can cross the blood-brain barrier. These characteristics are promising for development of in vivo amyloid probes similar to CG.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alzheimer Disease / diagnosis*
  • Amyloid beta-Peptides / analysis*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Benzoates*
  • Biomarkers / analysis
  • Biphenyl Compounds*
  • Blood-Brain Barrier
  • Coloring Agents* / metabolism
  • Female
  • Mice
  • Molecular Probes* / metabolism
  • Protein Binding


  • Amyloid beta-Peptides
  • Benzoates
  • Biomarkers
  • Biphenyl Compounds
  • Coloring Agents
  • Molecular Probes
  • chrysamine G