Structure determination of micelle-like intermediates in amyloid β-protein fibril assembly by using small angle neutron scattering

Open Access
Publisher Website
Google Scholar
Abstract
Increasing evidence supports the hypothesis that amyloid β-protein (Aβ) assembly is a key pathogenic feature of Alzheimer's disease. Thus, understanding the assembly process offers opportunities for the development of strategies for treating this devastating disease. In prior studies, Aβ was found to form micelle-like aggregates under acidic conditions. These structures exhibited an average observed hydrodynamic radius of 7 nm. They were found to be in rapid equilibrium with Aβ monomers or low molecular weight oligomers, and were centers of fibril nucleation. Here the technique of small angle neutron scattering has been used to determine the structure of these Aβ micelles. The data reveal that the micellar assemblies comprise 30–50 Aβ monomers and have elongated geometries. The best fit of the data to a uniform spherocylinder yields a radius ≈2.4 nm and cylinder length ≈11 nm. These structure parameters remain constant over more than a decade in concentration range. The concentration independence of the length of the cylindrical aggregate indicates the presence of an internal nonrepetitive structure that spans the entire length of the Aβ assembly.