DNP enhanced ssNMR of amyloid-beta precursors and fibrils

Alzheimer's disease is a neurodegenerative disorder that is strongly associated with high amyloid-beta concentration in the brain. A method that has been widely used to elucidate the structures formed by the amyloid-beta protein is solid-state nuclear magnetic resonance (ssNMR). The structures of amyloid-beta precursor structures as well as the fibrils which associate to form plaques may provide clues as to the mechanism of destruction caused by the amyloid-beta. My project will initially look to probe the interaction between amyloid-beta and lipid molecules that resemble those found in the membranes of cells using ssNMR. This will reveal the conformation of the protein as it interacts with the phospholipid molecules, with conditions being kept as physiological as possible. This experiment will be repeated with dynamic nuclear polarisation (DNP), which has been shown to significantly increase the signal intensity of ssNMR spectra. Depending on the results of these initial studies, membrane material will be taken from the brain of a mouse to monitor amyloid-beta conformation in more realistic physiological conditions. The molecular interactions of amyloid-beta under these conditions will provide clues as the mechanism by which the protein causes cell death in the brain.