β-amyloid fibril formation is promoted by step edges of highly oriented pyrolytic graphite

The aggregation of the amyloid-beta-protein (A beta) is an important step in the pathogenesis of Alzheimer's disease. As A beta fibrils are not found in all brain regions, endogenous factors may influence A beta fibril formation. In this study, atomic force microscopy was used to investigate the role of surface phenomena in directing amyloid aggregation. A beta 1-40 was applied to a surface of highly oriented pyrolytic graphite at a concentration of 0.5 mu M. Steps formed by edge-plane surface defects on the graphite were found to act as a template to promote the assembly of A beta into fibrils. Initially, after being deposited on the graphite surface, A beta had a uniform beaded morphology. However, after incubating (aging) the A beta on the surface for several hours, the A beta assembled along step edges to form linear aggregates. After more prolonged incubation, the linear A beta aggregates fused to form mature fibrils with a distinctive helical morphology. The results demonstrate that surface interactions can promote the aggregation of A beta into amyloid fibrils and they suggest that similar interactions could promote amyloid aggregation in vivo. (c) 2006 Wiley Periodicals, Inc.