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的发病和进展过程中，异常的β-淀粉样斑块的成分会导致结构和功能上的突触异常，从而导致突触丢失。突触丢失与AD患者认知功能下降的程度相关性最强。我的项目将遗传和分子标记技术与冷冻电子断层扫描相结合，以产生与AD相关的突触损伤的原位3D结构。获得这些天然的分子结构应该能够阐明与AD相关的导致突触恶化的机制，从而能够设计一种基于机制的AD治疗方法。

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.