Fibril formation in Alzheimer's disease is believed to result from the formation of unstable, slightly-unfolded protein conformations, resulting in a cascading aggregation process from monomers to oligomers to short filaments and eventually fully-developed amyloid fibrils. Recently, the prefibrillar intermediates have become viewed as the primary pathogenic species. To investigate amyloid intermediates we have developed two complementary approaches: a means to induce changes in protein folding and association in a controlled and photo-reversible manner, and a method to determine the in vitro conformation of associated proteins at relatively high resolution. These methods utilize the interaction of proteins with photosensitive surfactants that can be switched “on” or “off” with light. Light can be used to reversibly bind the surfactant to the protein, leading to photocontrol of protein conformation. Shape-reconstruction analysis applied to small angle neutron scattering (SANS) data is then employed to determine the conformation of protein oligomers. With the photo-actived surfactant, expanded corkscrew-like hexamers are observed. Converting to photo-passive surfactant causes hexamers to laterally aggregate, forming dodecamers with twisted conformations that eventually result in fully-developed fibrils. Together, these results provide the first direct observation of the mechanism of formation of the key intermediates in amyloid fibril formation, which could provide unique insight into the amyloidosis disease pathway.