Fibrillogenesis of synthetic amyloid-β peptides is dependent on their initial secondary structure

Abstract

Synthetic peptides containing the sequence of Alzheimer's amyloid-β peptide (Aβ) spontaneously form amyloid-like fibrils in vitro, and have been extensively used to study the factors that modulate fibrillogenesis. Contradictory observations have been reported regarding the neurotoxicity of A/3 and the influence of some Aβ-binding proteins on in vitro Aβ amyloid formation. In this study, we show that Aβ1–40 synthetic peptides obtained from different suppliers, have significantly distinct fibrillogenic properties. No differences were detected in the chemical structure or in the initial assembly state by mass spectroscopy, reverse-phase high performance liquid chromatography and denaturating or non-denaturing gel electrophoresis. However, there was a direct correlation between the ability of soluble peptides to form amyloid and their percentage of β-sheet structure, as determined by electron microscopy, fluorescence associated to thioflavine T bound to amyloid, and circular dichroism. The data suggest that the determinant factor of Aβ fibrillogenesis is the secondary structure adopted by the peptide in its soluble state.