Biophysical Comparison of Soluble Amyloid-β(1–42) Protofibrils, Oligomers, and Protofilaments

Some of the pathological hallmarks of the Alzheimer’s disease brain are senile plaques composed of insoluble amyloid-β protein (Aβ) fibrils. However, much of the recent emphasis in research has been on soluble Aβ aggregates in response to a growing body of evidence that shows that these species may be more neurotoxic than fibrils. Within this subset of soluble aggregated Aβ are protofibrils and oligomers. Although each species has been widely investigated separately, few studies have directly compared and contrasted their physical properties. In this work, we examined well-recognized preparations of Aβ(1–42) oligomers and protofibrils with multiangle (MALS) and dynamic (DLS) light scattering in line with, or following, size-exclusion chromatography (SEC). Multiple SEC–MALS analyses of protofibrils revealed molecular weight (Mw) gradients ranging from 200 to 2600 kDa. Oligomeric Aβ species are generally considered to be a smaller and more nascent than protofibrils. However, oligomer Mw values ranged from 2...