Alzheimer's disease (AD) is caused by abnormal deposition (fibrillation) of a 42-residue amyloid beta-protein (A beta 42) in the brain. During the process of fibrillation, the A beta 42 takes the form of protofibrils with strong neurotoxicity, and is thus believed to play a crucial role in the pathogenesis of AD. To elucidate the supramolecular structure of the A beta 42 protofibrils, the intermolecular proximity of the Ala-21 residues in the A beta 42 protofibrils was analyzed by C-13-C-13 rotational resonance experiments in the solid state. Unlike the A beta 42 fibrils, an intermolecular C-13-C-13 correlation was not found in the A beta 42 protofibrils. This result suggests that the beta-strands of the A beta 42 protofibrils are not in an in-register parallel orientation. A beta 42 monomers would assemble to form protofibrils with the beta-strand conformation, then transform into fibrils by forming intermolecular parallel beta-sheets. (C) 2012 Elsevier Inc. All rights reserved.