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

Increasing evidence supports the hypothesis that amyloid -protein (A ) 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, A 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 A 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 A micelles. The data reveal that the micellar assemblies comprise 30–50 A 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 A assembly.