Aurones serve as probes of beta-amyloid plaques in Alzheimer's disease.

Abstract

A novel series of aurone derivatives for in vivo imaging of beta-amyloid plaques in the brain of Alzheimer's disease (AD) were synthesized and characterized. When in vitro binding studies using Abeta(1-42) aggregates were carried out with aurone derivatives, they showed high binding affinities for Abeta(1-42) aggregates at the K(i) values ranging from 1.2 to 6.8 nM. When in vitro plaque labeling was carried out using double transgenic mice brain sections, the aurone derivatives intensely stained beta-amyiloid plaques. Biodistribution studies in normal mice after i.v. injection of the radioiodinated aurones displayed high brain uptake (1.9-4.6% ID/g at 2 min) and rapid clearance from the brain (0.11-0.26% ID/g at 60 min), which is highly desirable for amyloid imaging agents. The results in this study suggest that novel radiolabeled aurones may be useful amyloid imaging agents for detecting beta-amyloid plaques in the brain of AD.

• Authors: Masahiro Ono, Yoshifumi Maya, Mamoru Haratake, Kazuhiro Ito, Hiroshi Mori, Morio Nakayama
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 361 Issue 1 Pg. 116-21 (Sep 14 2007) ISSN: 0006-291X [Print] United States
• PMID: 17644062 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2-((4-aminophenyl)methylene)-5-iodo-3(2H)-benzofuranone
• 2-((4-dimethylaminophenyl)methylene)-5-iodo-3(2H)-benzofuranone
• 5-iodo-2-((4-methylaminophenyl)methylene)-3(2H)-benzofuranone
• Amyloid beta-Peptides
• Benzofurans
• Benzylidene Compounds
• Peptide Fragments
• Radiopharmaceuticals
• amyloid beta-protein (1-42)

Topics

• Alzheimer Disease (pathology)
• Amyloid beta-Peptides (analysis)
• Animals
• Benzofurans (chemistry, pharmacokinetics)
• Benzylidene Compounds (chemistry, pharmacokinetics)
• Brain (metabolism)
• Disease Models, Animal
• Mice
• Mice, Transgenic
• Microscopy, Fluorescence
• Peptide Fragments (analysis)
• Plaque, Amyloid (chemistry, pathology)
• Radiopharmaceuticals (chemistry, pharmacokinetics)