The in situ 3D molecular structure of Alzheimer's disease-associated pathology

阿尔茨海默病（AD）是一种无法治愈的晚期神经退行性疾病。在AD发病和进展过程中，异常β-淀粉样蛋白斑块的组分引起结构和功能性突触异常，导致突触丧失。突触丢失与AD患者的认知功能下降程度相关性最强。我的项目结合了基因和分子标记技术与冷冻电子断层扫描，以产生AD相关突触损伤的原位3D结构。获得这些天然的分子结构应该阐明AD相关的机制负责突触退化，使设计一个机制为基础的治疗AD。

Alzheimer's disease (AD) is a terminal neurodegenerative disorder with no cure. During AD pathogenesis and progression, the components of aberrant beta-amyloid plaques cause structural and functional synaptic abnormalities that result in synapse loss. Synaptic loss correlates the most strongly with the degree of cognitive decline in AD patients. My project combines genetic and molecular labelling techniques with cryo-electron tomography to produce in situ 3D structures of AD-related synaptic damage. Obtaining these native molecular structures should illuminate AD-relevant mechanisms responsible for synaptic deterioration, enabling the design of a mechanism-based treatment for AD.