This paper describes the synthesis, solution-phase biophysical studies, and X-ray crystallographic structures of hexamers formed by macrocyclic beta-hairpin peptides derived from the central and C-terminal regions of A beta, which bear "tails" derived from the N-terminus of A beta. Soluble oligomers of the beta-amyloid peptide, A beta, are thought to be the synaptotoxic species responsible for neurodegeneration in Alzheimer's disease. Over the last 20 years, evidence has accumulated that implicates the N-terminus of A beta as a region that may initiate the formation of damaging oligomeric species. We previously studied, in our laboratory, macrocyclic beta-hairpin peptides derived from A beta(16-22) and A beta(30-36), capable of forming hexamers that can be observed by X-ray crystallography and SDS-PAGE. To better mimic oligomers of full length A beta, we use an orthogonal protecting group strategy during the synthesis to append residues from A beta(1-14) to the parent macrocyclic beta-hairpin peptide 1, which comprises A beta(16-22) and A beta(30-36). The N-terminally extended peptides N+1, N+2, N+4, N+6, N+8, N+10, N+12, and N+14 assemble to form dimers, trimers, and hexamers in solution-phase studies. X-ray crystallography reveals that peptide N+1 assembles to form a hexamer that is composed of dimers and trimers. These observations are consistent with a model in which the assembly of A beta oligomers is driven by hydrogen bonding and hydrophobic packing of the residues from the central and C-terminal regions, with the N-terminus of A beta accommodated by the oligomers as an unstructured tail.