Morphological development of beta(1-40) amyloid fibrils

The Alzheimer's disease-related peptide beta(1-40) amyloid self-associates to form fibrils exhibiting a morphology characteristic of amyloidogenic pro teins. The mechanism of this fibrillization process has yet to be fully elu cidated. In this study we have immobilized the beta(1-40) amyloid to flat g old surfaces using thiol-based self-assembled monolayers. Atomic force micr oscopy reveals the presence of spherical units of beta(1-40) amyloid immedi ately following the initiation of fibrillization. Short fibrillar structure s, termed nascent fibrils, which appear to be formed by the association of these units are also present at this time point. At later time points exten ded, branching networks of fibrils are observed. Some fibrils exhibit a mor e beaded appearance and greater axial periodicity than others. No nascent f ibrils are seen to be present. We believe that these data identify an early fibril structure which could act as an intermediate in beta-amyloid fibril lization. The oligomeric units of which these nascent fibrils are comprised are also determined. (C) 1999 Academic Press.