Surfactant properties of Alzheimer's A beta peptides and the mechanism of amyloid aggregation.
The major proteinaceous component of amyloid deposits associated with Alzheimer's disease is a self-assembling 40-42-residue peptide, known as A beta, which is generated by the proteolytic processing of the amyloid precursor protein (Kang, J., Lemaire, H. G., Unterbeck, A., Salbaum, J. M., Masters, C. L., Grzeschik, K. H., Multhaup, G., Beyreuther, K., and Muller-Hill, B. (1987) Nature 325, 733-736; Haass, C., Hung, A. Y., Schlossmacher, M. G., Oltersdorf, T., Teplow, D. B., and Selkoe, D. J. (1993) Ann. N. Y. Acad. Sci. 695, 109-116; Estus, S., Golde, T. E., and Younkin S. G. (1992) Ann. N. Y. Acad. Sci. 674, 138-148) and is implicated as one of the causal factors in the pathology of the disease. A beta is now shown to display properties commonly associated with surfactants or detergents, which form micelles in solution. Increasing concentrations of A beta lower the surface tension of water up to a critical concentration, above which little further decrease in surface tension is observed. At concentrations above this critical concentration, increasing amounts of non-covalent aggregates of A beta are observed. A beta aggregation is also correlated with the formation of a hydrophobic environment that excludes water. The extent of this hydrophobic environment, as reflected by the partitioning of hydrophobic fluorescent probes, is much higher for the longer A beta 1-42 isoform, which may be more intimately associated with Alzheimer's disease pathology than A beta 1-40. Although the solution structure of A beta is not yet known, these results suggest that the structure of A beta has the same type of axial amphipathic organization as detergent molecules and that the same principles that govern micelle formation may also apply to A beta aggregation and amyloid fibril self-assembly.
Department of Molecular Biology and Biochemistry, University of California, Irvine 92717.
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Soreghan
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Kosmoski
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Glabe
D000544:Alzheimer Disease / Q000378:metabolism*; D000682:Amyloid / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry*; D013500:Surface Tension; D013501:Surface-Active Agents
D000682:Amyloid; D010455:Peptides; D013501:Surface-Active Agents