Solid-state NMR Reveals a Close Structural Relationship between Amyloid-β Protofibrils and Oligomers

We have studied tertiary contacts in protofibrils and mature fibrils of amyloid-beta (A beta) peptides using solid-state NMR spectroscopy. Although intraresidue contacts between Glu-22 and Ile-31 were found in A beta protofibrils, these contacts were completely absent in mature A beta fibrils. This is consistent with the current models of mature A beta fibrils. As these intramolecular contacts have also been reported in A beta oligomers, our measurements suggest that A beta protofibrils are structurally more closely related to oligomers than to mature fibrils. This suggests that some structural alterations have to take place on the pathway from A beta oligomers/protofibrils to mature fibrils, in agreement with a model that suggests a conversion of intramolecular hydrogen-bonded structures of A beta oligomers to the intermolecular stabilized mature fibrils (Hoyer, W., Gronwall, C., Jonsson, A., Stahl, S., and Hard, T. (2008) Proc. Natl. Acad. Sci. U.S.A. 105, 5099-5104).