Neuroimaging Biomarkers in Mouse Models of AD

AD 小鼠模型中的神经影像生物标志物

• 批准号: 8037624
• 负责人: ROBIA G PAUTLER
• 金额: $ 29.94万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-15 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8037624
• 关键词: Address; Age; Alzheimer' s Disease; Amyloid beta-Protein; Animals; Axon; Axonal Transport; Behavior; Behavioral; Biochemistry; Biological Markers; Data; Dementia; Deposition; Diagnostic; Disease; Disease Progression; Early Diagnosis; Endoplasmic Reticulum; Fluorescent Dyes; Fura-2; Goals; Grant; Hippocampus (Brain); Histology; Image; Immunotherapy; Impaired cognition; Ions; Magnetic Resonance Imaging; Manganese; Memantine; Memory Loss; Methodology; Microtubules; Modeling; Monitor; Movement; Mus; Neurites; Neurodegenerative Disorders; Neurofibrillary Tangles; Neuroglia; Neurons; Neurotoxins; Pathway interactions; Physiological; Property; R-flurbiprofen; Recovery; Research; Role; Symptoms; Synapses; Synaptic Cleft; System; Testing; Tg2576; Therapeutic; Tissues; Tracer; Travel; Treatment Efficacy; Weight; Work; age related; analog; basal forebrain; base; extracellular; hyperphosphorylated tau; improved; in vivo; light microscopy; mouse model; neuroimaging; news; novel; protein aggregate; response; tau Proteins; uptake; voltage

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.

描述（由申请人提供）：阿尔茨海默氏病（AD）是一种与年龄相关的神经退行性疾病，是痴呆症的主要原因之一，使痴呆症患者中有1％的人在60岁以下，超过40％以上的人85。这种疾病的症状是记忆力丧失和认知能力的逐渐下降。该疾病的特征是淀粉样蛋白β（AB）聚集体的细胞外沉积被称为斑块，这些斑块被营养不良的神经突和活化的神经胶质细胞以及由多磷酸化的TAU蛋白聚集体组成的细胞内神经纤维缠结。正如2006年2月的阿尔茨海默氏症研究论坛所详述的那样，广告研究中最关键的需求之一是鉴定生物标志物，不仅可以预测疾病，而且可以监测治疗的反应。在这个项目中，我们首先建议利用一种新型的MRI方法论，锰增强了MRI（MEMRI），我们帮助开发了为描述AB在体内轴突传输速率和突触前释放和突触后的启动和突触后摄取机械中的作用广告。其次，我们将测试MEMRI作为体内神经影像学诊断，以评估和可能很早就检测到AD小鼠模型中对治疗的反应。第三，我们将确定AB1-40，AB1-42或两种物种的组合是否有助于AD小鼠模型中轴突传输和突触前释放和突触后摄取机制的体内变化。