Aggregation of amyloid-beta (A beta) peptides is a characteristic pathological feature of Alzheimer's disease. We have exploited the relationship between solvent exposure and intrinsic fluorescence of a single tyrosine residue, Tyr(10), in the A beta sequence to probe structural features of the monomeric, oligomeric and fibrillar forms of the 42-residue A beta(1-42). By monitoring the quenching of Tyr(10) fluorescence upon addition of water-soluble acrylamide, we show that in A beta(1-42) oligomers this residue is solvent-exposed to a similar extent to that found in the unfolded monomer. By contrast, Tyrio is significantly shielded from acrylamide quenching in A beta(1-42) fibrils, consistent with its proximity to the fibrillar cross-beta core. Furthermore, circular dichroism measurements reveal that A beta(1-42) oligomers have a considerably lower beta-sheet content than the A beta(1-42) fibrils, indicative of a less ordered molecular arrangement in the former. Taken together these findings suggest significant differences in the structural assembly of oligomers and fibrils that are consistent with differences in their biological effects. (C) 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).