Neuroimaging Biomarkers in Mouse Models of AD

描述(申请人提供)：阿尔茨海默病(AD)是一种与年龄相关的神经退行性疾病，是导致痴呆症的主要原因之一，困扰着1%的60岁以下到超过40%的85岁以上的人。这种疾病的典型症状是记忆力丧失和认知能力的进行性下降。这种疾病的特点是细胞外沉积的淀粉样β蛋白(Ab)聚集体，即被营养不良的轴突和激活的胶质细胞包围的斑块，以及由过度磷酸化的tau蛋白聚集体组成的细胞内神经原纤维缠结。正如2006年2月的阿尔茨海默氏症研究论坛所详细说明的那样，AD研究中最关键的需求之一是识别不仅可以预测疾病而且可以监测治疗反应的生物标记物。在这个项目中，我们首先提出利用我们帮助开发的一种新的MRI方法--锰增强MRI(MEMRI)来描述AB在AD小鼠模型中对体内轴突运输速率和突触前释放和突触后摄取机制的作用。其次，我们将测试MEMRI作为体内神经成像诊断方法，以评估和潜在地检测AD小鼠模型的早期治疗反应。第三，我们将确定AB1-40、AB1-42或这两个物种的组合是否有助于在体内改变AD小鼠模型的轴突运输和突触前释放和突触后摄取机制。

DESCRIPTION (provided by applicant): Alzheimer's disease (AD) is an age-related, neurodegenerative disease that is one of the leading causes of dementia afflicting 1% of people under the age of 60 to more than 40% of people over the age of 85. The symptoms of this disease are typified by memory loss and a progressive decline of cognitive abilities. This disease is characterized by the extracellular deposition of amyloid-beta (Ab) aggregates known as plaques that are surrounded by dystrophic neurites and activated glial cells as well as intracellular neurofibrillary tangles that are comprised of hyperphosphorylated tau protein aggregates. As detailed in the February 2006 Alzheimer's Research Forum, one of the most critical needs in AD research is the identification of biomarkers that can not only predict disease but also monitor responses to treatment. In this project, we first propose to utilize a novel MRI methodology, Manganese Enhanced MRI (MEMRI) that we helped develop to delineate the role of AB on in vivo axonal transport rates and pre-synaptic release and post-synaptic uptake mechanisms in mouse models of AD. Second, we will test MEMRI as an in vivo neuroimaging diagnostic to assess and potentially detect very early on responses to treatment in mouse models of AD. Third, we will determine if Ab1- 40, Ab1-42 or the combination of the two species contributes to in vivo changes in axonal transport and pre- synaptic release and post-synaptic uptake mechanisms in mouse models of AD.