Neurotoxic protein oligomers — what you see is not always what you get

An increasing body of evidence suggests that soluble assemblies of amyloid proteins are the predominant neurotoxic species in many amyloid-related diseases. Consequently, the focus of research on pathologic mechanisms underlying amyloidoses has shifted from amyloid fibrils to oligomers. Biophysical characterization of oligomers is difficult due to their metastable nature. The most popular experimental method for detection of oligomers has been SDS-PAGE. However, we provide experimental evidence that SDS-PAGE is not a reliable method for characterization of amyloid protein oligomers and discuss alternative approaches. In addition, we discuss how inconsistent nomenclature has obfuscated our understanding of the process and products of protein assembly. The goals of this paper are to identify pitfalls associated with the methods and language used to study protein oligomers and to provide alternatives, thereby facilitating successful elucidation of the mechanisms controlling amyloid protein oligomer assembly ...