A beta 42 aggregation plays a central role in the pathogenesis of Alzheimer's disease. In addition to the insoluble fibrils that comprise the amyloid plaques, A beta 42 also forms soluble aggregates collectively called oligomers, which are more toxic and pathogenic than fibrils. Understanding the structure and dynamics of A beta 42 oligomers is critical for developing effective therapeutic interventions against these oligomers. Here we studied the structural dynamics of A beta 42 globulomers, a type of A beta 42 oligomers prepared in the presence of sodium dodecyl sulfate, using site-directed spin labeling. Spin labels were introduced, one at a time, at all 42 residue positions of A beta 42 sequence. Electron paramagnetic resonance spectra of spinlabeled samples reveal four structural segments based on site-dependent spin label mobility pattern. Segment-1 consists of residues 1-6, which have the highest mobility that is consistent with complete disorder. Segment-3 is the most immobilized region, including residues 31-34. Segment-2 and-4 have intermediate mobility and are composed of residues 7-30 and 35-42, respectively. Considering the inverse relationship between protein dynamics and stability, our results suggest that residues 31-34 are the most stable segment in A beta 42 oligomers. At the same time, the EPR spectral lineshape suggests that A beta 42 globulomers lack a well-packed structural core akin to that of globular proteins. (C) 2021 Elsevier Inc. All rights reserved.