Polymorphic Fibril Formation by Residues 10–40 of the Alzheimer’s β-Amyloid Peptide

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.