SignificanceOligomers of the β-amyloid peptide (Aβ) contribute to neurodegeneration in Alzheimer’s disease and are promising targets for therapies against Alzheimer’s disease. Understanding the structures and biology of Aβ oligomers is important for understanding the molecular basis of Alzheimer’s disease and for developing better therapeutics and diagnostics for the disease. Aβ oligomers are difficult to study because they are heterogeneous and unstable. To gain insights into Aβ oligomers and their role in neurodegeneration, we create, characterize, and compare two different well-defined chemical models of Aβ oligomers composed of different peptide fragments from Aβ that are constrained into β-hairpin conformations.