Amyloid beta peptide (Abeta) is a small peptide present in normal cells and aggregated Abeta is the main constituent of the extracellular amyloid plaques found in Alzheimer's disease (AD) brain. Recent studies suggest that soluble Abeta oligomers are neurotoxic rather than amyloid fibrils found in amyloid plaques. This study using multidimensional NMR spectroscopy and circular dichroism (CD) provides the first direct evidence that alterations in membrane structure can trigger the conversion of soluble alpha-helical monomeric Abeta into oligomeric Abeta in a beta-sheet conformation.