MR Microimaging of Alzheimer's Mouse Models

描述（由申请人提供）：本项目的总体目标是检查磁共振显微成像（MRM）对阿尔茨海默病小鼠模型的宏观神经解剖学表征的有用性。 AD的小鼠模型是更好地理解致病机制和开发新的治疗策略的有力一步。 在这些小鼠模型中，病理学的主要指标是淀粉样斑块。 然而，淀粉样蛋白沉积的时间和空间模式在各种AD小鼠模型中没有得到很好的表征。 此外，目前尚不清楚淀粉样蛋白沉积的不同转基因小鼠模型是否显示类似的淀粉样蛋白沉积模式。 淀粉样蛋白沉积的传统分析和其他解剖学分析，例如基于连续组织学切片的体积测量，对于有效地跟踪疾病的宏观演变和筛选治疗措施的效果所需的大量小鼠的分析都不是理想的。 在这项研究中，我们将MRM应用于AD小鼠模型和其他神经退行性疾病小鼠模型的表征。目的1是比较两种转基因小鼠AD模型的淀粉样斑块的三维分布和脑体积的变化。 假设：MRM可以有效地表征三维斑块分布和脑体积变化。 目的2：开发体内MRM，以在活体动物中重复目的1中的研究。 假设：淀粉样斑块的检测和体积测量可以在体内实现。 为了证实这些假设，将在4个不同年龄研究AD模型的2个小鼠品系。

DESCRIPTION (provided by applicant): The overall goal of this project is to examine usefulness of magnetic resonance microimaging (MRM) for the characterization of macroscopic neuroanatomy of mouse models of Alzheimer's disease. The mouse models of AD is a powerful step for better understanding of pathogenic mechanisms and in the development of new therapeutic strategies. In these mouse models, the primary indices of pathology are the amyloid plaques. However, the temporal and spatial pattern of amyloid deposition is not well characterized in the various mouse models of AD. Moreover, it is currently not known whether different transgenic mouse models of amyloid deposition shows similar pattern of amyloid deposition. The traditional analyses of amyloid deposition and other anatomical analyses such as volume measurements based on the serial histology sections, are not ideal for efficiently following the macroscopic evolution of the disease nor analysis of large number of mice required for screening the effects of therapeutic measures. In this study, we will apply the MRM to the characterization of mouse models of AD and other mouse models of neurodegenerative diseases. Aim 1 is to compare the three-dimensional distribution of amyloid plaques and changes in brain volumes of two transgenic mouse models of AD using ex vivo brains. Hypothesis: The MRM can efficiently characterize three-dimensional plaque distribution and brain volume changes. Aim 2: To develop in vivo MRM to replicate the study in Aim 1 in living animals. Hypothesis: The amyloid plaque detection and volume measurements can be achieved in vivo. To confirm these hypotheses, 2 mouse strains of the AD model will be studied at 4 different ages.