Aggregation of the amyloid P (AD) peptide yields both fibrillar precipitates and soluble oligomers, and is associated with Alzheimer's disease (AD). In vitro, Cu2+ and Zn2+ strongly bind AD and promote its precipitation. However, less is known about their interactions with the soluble oligomers, which are thought to be the major toxic species responsible for AD. Using fluorescence correlation spectroscopy to resolve the various soluble species of A beta, we show that low concentrations of Cu2+ (1 mu M) and Zn2+ (4 mu M) selectively eliminate the oligomeric population (within similar to 2 h), while Mg2+ displays a similar effect at a higher concentration (60 mu M). This uncovers a new aspect of A beta-metal ion interactions, as precipitation is not substantially altered at these low metal ion concentrations. Our results suggest that physiological concentrations of Cu2+ and Zn2+ can critically alter the stability of the toxic AD oligomers and can potentially control the course of neurodegeneration. (c) 2006 Elsevier Inc. All rights reserved.