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Molecular imaging ofAlzheimer amyloid

阿尔茨海默病淀粉样蛋白的分子成像

基本信息

批准号：
17300114
负责人：
MORI Hiroshi
金额：
$ 7.66万
依托单位：
Osaka City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17300114/
关键词：
Amyloid Alzheimer imagin senile placate PIB PET

项目摘要

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.

这项研究旨在开发和比较结合阿尔茨海默病大脑中淀粉样结构的化合物。我们首先开始苯乙烯，然后黄酮和橙酮结构作为淀粉样蛋白成像的有效配体。我们特别致力于将这些化合物与PIB进行比较，PIB是Pittsuberg大学研究小组开发的原始化合物。所有这些化合物模拟硫磺素作为母体结构，并检查了它们从脑组织的高掺入和排除。其中一个主要问题是没有检测到任何阳性信号的PIB转基因小鼠命名为Tg2576，虽然PIB表现出美丽的图像与AD患者。通过对APP 23和Tg2576 × PS 1双转基因小鼠两个品系的比较，探索了这一基础。我们首先再现了Tg2576线的负信号，但成功地检测到APP 23的强PIB信号。然后我们比较了PET成像后的两种脑组织。这两种组织都显示出许多淀粉样蛋白斑块，足以用淀粉样蛋白抗体检测到。我们用几种淀粉样蛋白抗体检查了组织，最终找到了一种区分APP 23和Tg2576的抗体。该抗体被认为特异性识别淀粉样蛋白第三个残基上的焦谷氨酸。这一修正最初是由我发现的，目前的结果清楚地解释了加速度动物模型与人类老年AD患者之间的差异。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Cerebral vascular accumulation of Dutch-type A1342, but not wild-type A1342, in hereditary cerebral hemorrhage with amyloidosis, Dutch type.

荷兰型淀粉样变性遗传性脑出血患者脑血管中聚集了荷兰型 A1342，但野生型 A1342 没有。

DOI：
发表时间：
2007
期刊：
J. Neurosci. Res 85
影响因子：
0
作者：
Nishitsuji;K.;Tomiyama;T.;Ishibashi;K.;Kametani;F.;Ozawa;K.;Okada;R.;Maat-Schieman;M.L.;Roos;R.A.C.Iwai;K.;Mori;H
通讯作者：
H

Regulation of tau exon 10 splicing by a double stem-loop structure in mouse intron 10

小鼠内含子 10 中双茎环结构对 tau 外显子 10 剪接的调节

DOI：
发表时间：
2005
期刊：
FEBS Lett 579
影响因子：
0
作者：
Yamashita;T.;Tomiyama;T.;Li;Q.;Numata;H.;Mori;H
通讯作者：
H

Absence of synaptophysin near cortical neurons containing oligomer Aβ in Alzheimer's disease brain

DOI：
10.1002/jnr.20952
发表时间：
2006-08-15
期刊：
JOURNAL OF NEUROSCIENCE RESEARCH
影响因子：
4.2
作者：
Ishibashi, Ken-Ichi;Tomiyama, Takami;Mori, Hiroshi
通讯作者：
Mori, Hiroshi

Structure-activity relationship of chalcones and related derivatives as ligands for detecting of β-amyloid plaques in the brain

哈尔酮及相关衍生物作为配体检测大脑β-淀粉样斑块的构效关系

DOI：
发表时间：
2007
期刊：
Bioorganic and Medicinal Chemistry 15
影响因子：
0
作者：
M. Ono;M. Hori;M. Haratake;T. Tomiyama;H. Mor;M. Nakayama
通讯作者：
M. Nakayama

Novel Benzofuran Derivatives for PET Imaging of β-Amyloid Plaques in Alzheimer's disease Brains.

用于阿尔茨海默病大脑中 β-淀粉样斑块 PET 成像的新型苯并呋喃衍生物。

DOI：
发表时间：
2006
期刊：
J. Med. Chem. 49(9)
影响因子：
0
作者：
Ono;M.;Kawashima;H.;Nonaka;A.;Kawai;T.;Haratake. M;Mori;H.;Kung;M-P.;Kung;H.F.;Saji;H.;and Nakayama;M.
通讯作者：
M.