MRI OF ALZHEIMER'S PATHOLOGY IN BRAINS OF TRANSGENIC MICE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 阿尔茨海默病(AD)是导致老年人痴呆的最常见原因。AD的主要病理特征是淀粉样斑块和神经原纤维缠结，大多数业内人士认为最终导致临床AD的始发事件集中在淀粉样β蛋白代谢的紊乱。通过在小鼠基因组中插入一个或多个与淀粉样蛋白代谢紊乱相关的导致早发性家族性AD的突变，建立了AD的小鼠模型。在这些转基因小鼠中，类人淀粉样斑块的形成随着年龄的增长而急剧增加。减少人类淀粉样蛋白是一个主要的治疗目标，AD转基因小鼠可以对这一生物学进行对照研究。最近的工作表明，在高磁场(9.4T)下，可以使用体内磁共振显微成像(MRMI)检测到小至35？m的淀粉样斑块。此外，在这些转基因小鼠中，可以在高磁场下使用单体素1H磁共振波谱(1HMRS)检测到与人类AD患者相似的代谢物浓度随年龄的变化。这些基于磁共振的技术为致力于在转基因疾病模型中研究AD生物学的科学界提供了一套新的工具。例如，一个明显的应用是评估疾病进展的治疗改进。在这篇综述的最后，作者包括了一项先导研究的结果，该研究证明了使用MRMI检测AD转基因小鼠斑块进展的治疗性修饰的可行性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Cardinal pathologic features of AD are amyloid plaques and neurofibrillary tangles, and most in the field believe that the initiating events ultimately leading to clinical AD center on disordered metabolism of amyloid beta protein. Mouse models of AD have been created by inserting one or more human mutations associated with disordered amyloid metabolism and that cause early onset familial AD into the mouse genome. Human-like amyloid plaque formation increases dramatically with age in these transgenic mice. Amyloid reduction in humans is a major therapeutic objective, and AD transgenic mice allow controlled study of this biology. Recent work has shown that amyloid plaques as small as 35 ¿m can be detected using in vivo magnetic resonance microimaging (MRMI) at high magnetic field (9.4 T). In addition, age-dependent changes in metabolite concentration analogous to those that have been identified in human AD patients can be detected in these transgenic mice using single-voxel 1H magnetic resonance spectroscopy (1H MRS) at high magnetic field. These MR-based techniques provide a new set of tools to the scientific community engaged in studying the biology of AD in transgenic models of the disease. For example, an obvious application is evaluating therapeutic modification of disease progression. Toward the end of this review, the authors include results from a pilot study demonstrating feasibility of using MRMI to detect therapeutic modification of plaque progression in AD transgenic mice.