Small angle X-ray scattering analysis of Cu super(2+)-induced oligomers of the Alzheimer's amyloid beta peptide

Research into causes of Alzheimer's disease and its treatment has produced a tantalising array of hypotheses about the role of transition metal dyshomeostasis, many of them on the interaction of these metals with the neurotoxic amyloid- beta peptide (A beta ). Here, we have used small angle X-ray scattering (SAXS) to study the effect of the molar ratio, Cu super(2+)/A beta , on the early three-dimensional structures of the A beta sub(1-40) and Cu super(2+)/A beta sub(1-42) peptides in solution. We found that at molar ratios of 0.5 copper to peptide A beta sub(1-40) aggregated, while A beta sub(1-42) adopted a relatively monodisperse cylindrical shape, and at a ratio of 1.5 copper to peptide A beta sub(1-40) adopted a monodisperse cylindrical shape, while A beta sub(1-42) adopted the shape of an ellipsoid of rotation. We also found, viain-line rapid mixing SAXS analysis, that both peptides in the absence of copper were monodisperse at very short timeframes (