An improved method for generating consistent soluble amyloid-beta oligomer preparations for in vitro neurotoxicity studies

Soluble A beta oligomers are recognized as playing a key role in Alzheimer's disease (AD) pathophysiology. Despite their significance, many investigators encounter difficulty generating reliable preparations for in vitro and in vivo experiments. Solutions of A beta are often unstable and soluble conformer profiles inconsistent. In this study we describe detailed methods for preparing A beta oligomers that are stable for several weeks and are enriched for low and high molecular weight oligomeric forms, including the 56-kDa form, a conformer implicated in AD-related cognitive impairment. We characterize their structural and functional properties using Western blot, dot blot, atomic force microscopy, Thioflavine T fluorescence, and primary neuronal culture toxicity assays. These synthetic preparations should prove valuable to many studying AP-mediated mechanisms underlying AD. (C) 2010 Elsevier B.V. All rights reserved.