Linking Plaque Shapes to Amyloid Structures in Alzheimer’s Disease

This project will determine the structural differences of amyloid-ß (Aß) in various plaques in Alzheimer’s disease to identify potential links between plaque morphology and disease progression and to aid in the development of novel diagnostic tools. 

Alzheimer’s disease is marked by abnormal deposits of Aß and tau proteins in the brain, leading to memory loss and cognitive decline. Using cutting-edge cryo-electron microscopy, we aim to study the structures of Aß in different plaque types and brain regions. Our research focuses on understanding how these structural variations contribute to disease progression, especially in cases linked to genetic risk factors like APOE e4. This work could uncover new diagnostic markers and therapeutic targets, advancing efforts to combat Alzheimer’s disease and related disorders.

By analyzing the structural variations among different plaque types, we aim to identify potential links between plaque morphology and disease progression and determine which factors determine the formation of distinct Aß folds. This knowledge is crucial to develop relevant model systems for disease and ultimately to better understand the molecular mechanisms of disease. This work may open new avenues for the identification of specific structures important for binding of ligands designed for in vivo imaging and potential therapeutic approaches.

This study will uncover how different amyloid plaque structures contribute to Alzheimer’s disease progression, especially in individuals with genetic risk factors like APOE e4. These insights could lead to improved diagnostic imaging tools and targeted therapies, ultimately helping to better identify, monitor, and treat those at risk.