Amyloid-beta & Alzheimer's Disease

Alzheimer’s Disease is characterized by large toxic fibrils and plaques in the brain. Amyloid-beta, a small, naturally occurring protein, is the major component of these fibrils and plaques. In order to understand the formation of the toxic forms of the protein, we would like to have a picture of Amyloid-beta in the free state, when not part of these fibrils or smaller aggregates. This is particularly difficult because unlike most proteins, which adopt a single, well-folded structure, Amyloid-beta is very flexible and constantly changes shape. However, we can use a combination of physics based computer simulations and biological NMR spectroscopy to understand Amyloid-beta structure and how this structure may influence toxicity and disease.