(199a) Searching for Oligomers during Insulin Fibrillation

Recent reports suggest that small oligomers consisting of between 4 and 8 monomers could be the pathogenic element associated with many amyloid fibril diseases such as Alzheimers, Parkinson's, Huntingtons and many other aging-related diseases. Because of the presence of the fibers and other large aggregates, chromatographic methods are limited in analyzing these complex fibrillation feeds. Using insulin as a model amyloid system, we describe a simple yet elegant method ? cascade membrane filtration ? to fractionate the fibrils from a series of smaller and smaller oligomers. This, together with atomic force microscopy, allows one to follow various molecular aggregated components, possibly oligomer, during the formation of fibrils. Comparison of these results with predictions using a new nucleation and growth model will be attempted.