Research Project
Grant-in-Aid for Scientific Research (B)
This study aimed to develop and compare chemical compounds which bind amyloid structure in brains with Alzheimer's disease. We first started stylbene then flavone and aurone structures as potent ligands for amyloid imaging. We dedicated particularly to compare these compounds with PIB that is well established as the original compound developed by Pittsuberg University research group. All of these compounds mimic thioflavine as the mother structure and examined their high incorporation and exclusion from the brain tissue. One of the major problem was not to detect any positive signal of PIB for transgenic mice named Tg2576 although PIB demonstrated the beautiful imaging for patients with AD. We explored this base by comparison of two line of transgenic mice of APP23 and Tg2576 x PS 1 double transgenic mice. We first reproduced the negative signal for Tg2576 line but succeeded in detect the strong PIB signal for APP23. Then we compared both brain tissues after PET imaging. Both tissues show many amyloid plaques enough to be detected with amyloid antibodies. We examined tissues with several amyloid antibodies and finally reached to find one antibody to distinguish APP23 from Tg2576. This antibody was supposed to specifically recognize pyroglutamate at the third residue of amyloid protein. This post modification was originally found by me. The present result clearly explains the discrepancy between acceleration animal model and human aged patients with AD.
All 2008 2007 2006 2005 Other
All Journal Article (51 results) (of which Peer Reviewed: 25 results) Patent(Industrial Property Rights) (4 results)
Ann. Neurol. (In press)(In press)
Ann.Neurol. (In press)
Bioorg. Med. Chem. 15
Pages: 6388-6396
Biochem. Biophys. Res. Commun. 361
Pages: 116-121
J. Neurosci. Res. 85
Pages: 2917-2923
NeuroReport 18
Pages: 1083-1087
Brain 130(Pt5)
Pages: 1386-1394
J. Neurosci. 27
Pages: 10957-10968
Bioorg. Med. Chem 15
Biochem. Biophys. Res. Commun 361
J. Neurosci. Res 85
Brain 130(Pt 5)
Bioorg.Med.Chem 15
Biochem.Biophys.Res.Commun 361
J.Neurosci.Res. 85
J.Neurosci. 27
Brain in press
J. Med. Chem. 49(9)
Pages: 2725-2730
Biochem. Biophys. Res. Couuuun. 351(3)
Pages: 602-611
Hippocampus 17(2)
Pages: 98-102
J. Neurosci. 26
Pages: 3514-3523
J. Neurosci. Res. 84
Pages: 632-636
J. Med. Chem 49
Biochem. Biophys. Res. Commun 351
Hippocampus 17
J. Neurosci 26
J. Neurosci. Res 84
Biochem. Biophys. Res. Commun. 351(3)
FEBS Lett. 579
Pages: 241-244
Nucl. Med. Biol. 32(4)
Pages: 329-335
FEBS Lett. 579(25)
Pages: 5704-5712
J. Med. Chem. 48(23)
Pages: 7253-7260
J. Neurochem. 94
Pages: 425-439
Aiu. J. Alzheimers Dis. Other Demen. 20(5)
Pages: 315-8
FEBS Lett 579
Nucl. Ned. Biol 32
J. Med. Chem 48
J. Neurochem 94
Am. J. Alzheimers Dis. Other Demen 20(5)
Nucl.Med.Biol. 32(4)
J.Med.Chem. 48(23)
Ann. Neurol (In press)