ApoE and cytokines: In vivo effects on AD-like pathology

描述（由申请人提供）：为了充分了解阿尔茨海默病（AD）发病过程中发生的事件，了解所涉及的各种细胞类型和分子与疾病的病理学标志之间的关系至关重要。更好地理解这些复杂关系的一种方法是在体内以真实的时间将它们可视化，同时阻断或增强可能参与这些关系的特定分子的功能。为此，我们建议使用体内多光子成像的小鼠大脑含有AD样病理可视化小胶质细胞，神经元和神经元过程之间的相互作用在真实的时间.这将使我们能够确定AD大脑环境中存在的特定分子如何影响这些细胞类型的结构和功能。我们假设apoE和聚集的β-淀粉样蛋白之间的相互作用是动态的，并调节小胶质细胞的运动和细胞因子的释放，导致神经元过程的持续损伤。阐明如何小胶质细胞的形态和运动性以及神经元损伤的影响聚集β-淀粉样蛋白，载脂蛋白E和特定的细胞因子产生的小胶质细胞将在体内进行探索。

DESCRIPTION (provided by applicant): In order to fully appreciate events that occur during Alzheimer's disease (AD) pathogenesis it is critical to understand the relationships between the various cell types and molecules involved and the pathological hallmarks of the disease. One way to better understand these complex relationships is to visualize them in vivo, in real time, while blocking or augmenting the function of particular molecules that are potentially involved in these relationships. To this end, we propose to use in vivo multiphoton imaging of a murine brain containing AD- like pathology to visualize interactions between microglia, neurons, and neuronal processes in real time. This will enable us to determine how specific molecules present within the milieu of the AD brain affect the structure and function of these cell types. We hypothesize that the interaction between apoE and aggregated beta-amyloid is dynamic and regulates microglial motility and cytokine release that results in ongoing injury to neuronal processes. Elucidation of how microglial cell morphology and motility as well as neuronal injury are affected by aggregated beta-amyloid, apoE and specific cytokines produced by microglia will be explored in vivo.