SURFACTANT PROPERTIES OF ALZHEIMERS A-BETA PEPTIDES AND THE MECHANISMOF 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 amy loid precursor protein (Kang, J., Lemaire, H. G., Unterbeck, A., Salba um, 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) an d is implicated as one of the causal factors in the pathology of the d isease. A beta is now shown to display properties commonly associated with surfactants or detergents, which form micelles in solution. Incre asing concentrations of A beta lower the surface tension of water up t o a critical concentration, above which little further decrease in sur face tension is observed. At concentrations above this critical concen tration, increasing amounts of non-covalent aggregates of A beta are o bserved. A beta aggregation is also correlated with the formation of a hydrophobic environment that excludes water. The extent of this hydro phobic environment, as reflected by the partitioning of hydrophobic fl uorescent probes, is much higher for the longer A beta 1-42 isoform, w hich may be more intimately associated with Alzheimer's disease pathol ogy 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 an d that the same principles that govern micelle formation may also appl y to A beta aggregation and amyloid fibril self-assembly.