Small angle X-ray scattering analysis of Cu 2+ -induced oligomers of the Alzheimer's amyloid β 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-β peptide (Aβ). Here, we have used small angle X-ray scattering (SAXS) to study the effect of the molar ratio, Cu 2+ /Aβ, on the early three-dimensional structures of the Aβ 1–40 and Cu 2+ /Aβ 1–42 peptides in solution. We found that at molar ratios of 0.5 copper to peptide Aβ 1–40 aggregated, while Aβ 1–42 adopted a relatively monodisperse cylindrical shape, and at a ratio of 1.5 copper to peptide Aβ 1–40 adopted a monodisperse cylindrical shape, while Aβ 1–42 adopted the shape of an ellipsoid of rotation. We also found, via in-line rapid mixing SAXS analysis, that both peptides in the absence of copper were monodisperse at very short timeframes (