High-resolution probing of early events in amyloid-β aggregation related to Alzheimer's disease
Bikash R. Sahoo, Sarah J. Cox, Ayyalusamy Ramamoorthy
Abstract
F based NMR experiments to identify the formation of small size early intermediates and to obtain their structures, and dock-lock mechanism of fiber growth at atomic-resolution are discussed. In addition, the use of proton-detected magic angle spinning (MAS) solid-state NMR experiments to obtain high-resolution insights into the aggregation pathways and structures of large oligomers and other aggregates is also presented. We expect these NMR based studies to be valuable for real-time monitoring of the depletion of monomers and the formation of toxic oligomers and high-order aggregates under a variety of conditions, and to solve the high-resolution structures of small and large size oligomers for most amyloid proteins, and therefore to develop inhibitors and drugs.