FIBRILLOGENESIS OF SYNTHETIC AMYLOID-BETA PEPTIDES IS DEPENDENT ON THEIR INITIAL SECONDARY STRUCTURE

Synthetic peptides containing the sequence of Alzheimer's amyloid-beta peptide (A beta) spontaneously form amyloid-like fibrils in vitro, an d have been extensively used to study the factors that modulate fibril logenesis. Contradictory observations have been reported regarding the neurotoxicity of A beta and the influence of some A beta-binding prot eins on in vitro A beta amyloid formation. In this study, we show that A beta 1-40 synthetic peptides obtained from different suppliers, hav e significantly distinct fibrillogenic properties. No differences were detected in the chemical structure or in the initial assembly state b y mass spectroscopy, reverse-phase high performance liquid chromatogra phy and denaturating or non-denaturing gel electrophoresis. However, t here was a direct correlation between the ability of soluble peptides to form amyloid and their percentage of beta-sheet structure, as deter mined by electron microscopy, fluorescence associated to thioflavine T bound to amyloid, and circular dichroism. The data suggest that the d eterminant factor of A beta fibrillogenesis is the secondary structure adopted by the peptide in its soluble state.