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

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.