Neuroimaging Biomarkers in Mouse Models of AD

描述（由申请人提供）：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岁以下人群到超过40%的85岁以上人群。这种疾病的典型症状是记忆丧失和认知能力的逐渐下降。这种疾病的特征是淀粉样蛋白- β (Ab)聚集体称为斑块的细胞外沉积，被营养不良的神经突和活化的胶质细胞包围，以及细胞内由过度磷酸化的tau蛋白聚集体组成的神经原纤维缠结。正如2006年2月的阿尔茨海默病研究论坛所详述的那样，阿尔茨海默病研究中最关键的需求之一是确定不仅可以预测疾病而且可以监测治疗反应的生物标志物。在这个项目中，我们首先提出利用一种新的MRI方法，锰增强MRI (MEMRI)，我们帮助开发描绘AB在AD小鼠模型体内轴突运输速率和突触前释放和突触后摄取机制中的作用。其次，我们将测试MEMRI作为一种体内神经影像学诊断，以评估和潜在地检测AD小鼠模型对治疗的早期反应。第三，我们将确定Ab1- 40、Ab1-42或两者的结合是否有助于AD小鼠模型中轴突转运、突触前释放和突触后摄取机制的体内变化。

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.