Preparation and Fractionation of Heterogeneous Aβ42 Oligomers with Different Aggregation Properties

Deposition of amyloid-β (Aβ) aggregates in the form of amyloid plaques is a central feature of Alzheimer's disease. The end products of Aβ aggregation are amyloid fibrils. Soluble Aβ aggregates called oligomers are also formed either on or off the pathway of fibril formation. The amyloid fibrils from different clinical subtypes of Alzheimer's disease have been found to adopt different structures, a phenomenon called fibril polymorphism. Meanwhile, different types of Aβ oligomers have also been found. Recently, it has been shown that different types of Aβ42 oligomers may form fibrils of different structures, linking oligomer heterogeneity to fibril polymorphism. In this chapter, we describe methods to prepare heterogeneous Aβ42 oligomers and to quantify the concentration of these oligomers at a low micromolar range using a fluorescamine method. Fractionation of these oligomers by size using ultrafiltration filters allows for the formation of Aβ42 fibrils with different structural properties.