基于多模态影像学研究Aβ沉积对AD神经功能网络连接的影响机制

项目名称： 基于多模态影像学研究Aβ沉积对AD神经功能网络连接的影响机制

项目编号： No.81471720

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 王晓明

作者单位： 中国医科大学

项目金额： 72万元

中文摘要： 阿尔茨海默病（AD）是以记忆和其他高级认知功能下降为特征，基于神经影像的脑结构和功能网络的研究证实AD患者的记忆和认知功能下降是由于脑结构和功能连接通路等结构和网络功能整合发生异常所致。AD的主要病理改变是Aβ沉积，Ach、Glu、DA等神经递质在Aβ作用下可能对神经元活性产生作用，使神经网络功能连接发生变异。因此，本研究针对Aβ沉积与神经元信号网络变化的相互关系开展研究。本研究通过双转基因小鼠（APP/PS1）模拟AD的病理变化，采用多模态的11C、18F标记的PET分子显像针对Aβ及神经递质进行特异性显像，结合fMRI研究老年斑中的铁沉积，并与脑内神经递质及其代谢、受体等变化以及相应分子生物学指标（Fe2+、Aβ、GLTs等）结果进行相关研究，评估Aβ沉积发生过程中与铁离子沉积、EAAs等神经信号分子之间的相互作用，以期明确Aβ异常沉积的发生机制及其对神经功能网络连接的变异所起的作用。

中文关键词： 多模态分子影像学；阿尔茨海默病；正电子放射性药物；淀粉样蛋；磁敏感

英文摘要： Alzheimer's disease (AD) is characterized by the decline of memory and other cognitive. It has been advanced confirmed that the decline in memory and cognitive function in patients with AD due to cerebral structure and the function of the brain connecting passage structural and functional integration of networks, such as the occurrence of abnormality based on the neural imaging of cerebral and functionnal netwok studies. The main pathological changes of AD is Aβ deposition, Ach, Glu, DA and other neurotransmitters may have an effect on neuronal activity under the action of Aβ, so that the neural network functional connectivity mutates. Therefore , this study focus on the relationship between Aβ deposition and neuronal signaling network changes. In this study, by using double transgenic mice (APP/PS1) to simulate the pathological changes of AD , multimodality 11C, 18F-labeled PET molecular imaging for Aβ and neurotransmitter specilly, combinning with senile plaques iron deposition of fMRI study , and with brain neurotransmitters and their metabolites, changes of receptors and the corresponding molecular markers (Fe2+, Aβ, GLTs, etc. ) related to the results of a study to assess the interactions on the process of Aβ deposition occurs with iron ions, EAAs, etc, in order to define the mechanism of Aβ abnormal deposition and the role of variation in neurological function of network connection.

英文关键词： multimodality molecular imaging;Alzheimer's disease;Positron radiopharmaceuticals;Amyloid;Susceptibility