Polymorphic fibril formation by residues 10-40 of the Alzheimer's β-amyloid peptide

Abstract

We report investigations of the morphology and molecular structure of amyloid fibrils comprised of residues 10-40 of the Alzheimer's β-amyloid peptide (Aβ10-40), prepared under various solution conditions and degrees of agitation. Omission of residues 1-9 from the full-length Alzheimer's β-amyloid peptide (Aβ1-40) did not prevent the peptide from forming amyloid fibrils or eliminate fibril polymorphism. These results are consistent with residues 1-9 being disordered in Aβ1-40 fibrils, and show that fibril polymorphism is not a consequence of disorder in residues 1-9. Fibril morphology was analyzed by atomic force and electron microscopy, and secondary structure and inter-side-chain proximity were probed using solid-state NMR. Aβ1-40 fibrils were found to be structurally compatible with Aβ10-40:Aβ1-40 fibril fragments were used to seed the growth of Aβ10-40 fibrils, with propagation of fibril morphology and molecular structure. In addition, comparison of lyophilized and hydrated fibril samples revealed no effect of hydration on molecular structure, indicating that Aβ10-40 fibrils are unlikely to contain bulk water. © 2006 by the Biophysical Society.