The Effect of a Membrane Mimicking Detergent on Alzheimer's Amyloid Peptide Aggregation Studied by EPR

Abstract

The aggregation of the β-Amyloid (Aβ) peptide into fibrils is the chief indicator of Alzheimer's disease. However, it seems that small, oligomeric aggregates, rather than fully formed fibrils could be the toxic species. Aβ -membrane interaction could also have an effect, so here effect of the membrane-mimicking detergent SDS is studied.We measure, by spin-label-mobility EPR, Aβ aggregation at different SDS concentrations. It monitors all peptide in the sample and is not limited to particular aggregate sizes. The high-SDS form found (C) is consistent with the one-peptide/micelle model [1-2]. In the absence of SDS (A) the high concentration of Aβ (0.55 mM) most certainly enforces fibrils. At intermediate SDS (B), EPR reveals an increase in particle size suggestive of oligomer formation, eventually involving detergents. Thus a first glimpse into the behavior of SDS at sub-CMC (Critical Micelle Concentration) SDS concentrations, where high resolution techniques, such as NMR, fail because of particle size limitation, [1-2] are accessible.View Large Image | View Hi-Res Image | Download PowerPoint Slide[1] FEBS, Wahlstrom et al. (2008) 275: 5117-5128.[2] J. Biomol NMR, Juri et al. (2007) 39: 63-72.