Oligomers of the beta-amyloid peptide A beta have emerged as important contributors to neurodegeneration in Alzheimer's disease. Mounting evidence suggests that A beta trimers and higher-order oligomers derived from trimers have special significance in. the early stages of Alzheimer's disease. Elucidating the structures of these trimers and higher-order oligomers is paramount for understanding their role in neurodegeneration. This paper describes the design, synthesis, X-ray crystallographic structures, and biophysical and biological properties of two stabilized tit-Ters derived from the central and C-terminal regions of A beta. These triangular trimers are stabilized through three disulfide cross-links between the:monomer: subunits, The X-ray crystallographic structures reveal that the stabilized timers assemble hierarchically to form hexamers, dodecamers, and annular porelike structures. Solution-phase biophysical studies reveal that-the stabilized trimers assemble in solution to form oligomers that recapitulate some of the higher-order assemblies observed crystallographically. The stabilized trimers share many of the biological characteristics of oligomers of full-length A beta, including toxicity toward a neuronally derived human cell line, activation of caspase-3 mediated apoptosis, and reactivity with the oligomer-specific antibody All. These studies support the biological significance of the triangular trimer assembly of A beta beta-hairpins and may offer a deeper understanding of the molecular basis of Alzheimer-'s disease.