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 (A β 10–40), prepared under various solution conditions and degrees of agitation. Omission of residues 1–9 from the full-length Alzheimer’s β-amyloid peptide (A β 1–40) did not prevent the peptide from forming amyloid fibrils or eliminate fibril polymorphism. These results are consistent with residues 1–9 being disordered in A β 1–40 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. A β 1–40 fibrils were found to be structurally compatible with A β 10–40: A β 1–40 fibril fragments were used to seed the growth of A β 10–40 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 A β 10–40 fibrils are unlikely to contain bulk water.