Structural transitions associated with the interaction of Alzheimer β-amyloid peptides with gangliosides

Alzheimer's disease is characterized pathologically by the presence of neurofibrillary tangles and amyloid plaques. The principal component of the plaque is the beta-amyloid peptide (A beta), a 39-43-resiure peptide. The conformational change required for the conversion of soluble peptide into amyloid fabrils is modulated by pH, A beta concentration, addition of kinetic and thermodynamic enhancers, and alterations in the primary sequence of A beta. We report here the ability of gangliosides to induce an alpha-helical structure in A beta and thereby diminish fibrillogenesis, Circular dichroism and a fluorescence dye release assay data indicate that gangliosides interact with and induce alpha-helix formation in A beta. We find that the sialic acid moiety of gangliosides is necessary for the induction of alpha-helical structure. Differences in the amount and the position of the sialic acid on the carbohydrate backbone also affect the conformational switch. The A beta-ganglioside interaction at pH 7.0, monitored by CD, is stable over time and resistant to high concentrations of NaCl. The induction of alpha-helical structure is greater with A beta 1-40 than A beta 1-42. The ability of gangliosides to sequester A beta from fibril formation was also evaluated by electron microscopy.