In vitro preparation of prefibrillar intermediates of amyloid-beta and alpha-synuclein.

Elucidating the structural properties of early intermediates (protofibrils) on the fibril formation pathway of Abeta and alpha-synuclein, the structural relationship among the different intermediates and their relationship to the structure of the amyloid fibrils is critical for understanding the roles of amyloid fibril formation in the pathogenesis of Alzheimer's and Parkinson's diseases. In this chapter we discuss several methods, developed by different laboratories, that enable the preparation and stabilization of amyloid-beta and alpha-synuclein protofibrillar species of defined morphologies for biochemical, biophysical and toxicity studies.