Aggregation of the A beta(1-40) peptide is linked to the development of extracellular plaques characteristic of Alzheimer's disease. While previous studies commonly show the A beta(1-40) is largely unstructured in solution, we show that A beta(1-40) can adopt a compact, partially folded structure. In this structure (PDB ID: 2LFM), the central hydrophobic region of the peptide forms a 3(10) helix from H13 to D23 and the Nand C-termini collapse against the helix due to the clustering of hydrophobic residues. Helical intermediates have been predicted to be crucial on-pathway intermediates in amyloid fibrillogenesis, and the structure presented here presents a new target for investigation of early events in A beta(1-40) fibrillogenesis. (C) 2011 Elsevier Inc. All rights reserved.