J. Mclaurin et al., STRUCTURAL TRANSITIONS ASSOCIATED WITH THE INTERACTION OF ALZHEIMER BETA-AMYLOID PEPTIDES WITH GANGLIOSIDES, The Journal of biological chemistry, 273(8), 1998, pp. 4506-4515
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 pe
ptide. The conformational change required for the conversion of solubl
e peptide into amyloid fabrils is modulated by pH, A beta concentratio
n, addition of kinetic and thermodynamic enhancers, and alterations in
the primary sequence of A beta. We report here the ability of ganglio
sides to induce an alpha-helical structure in A beta and thereby dimin
ish 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 gang
liosides is necessary for the induction of alpha-helical structure. Di
fferences in the amount and the position of the sialic acid on the car
bohydrate backbone also affect the conformational switch. The A beta-g
anglioside 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 ab
ility of gangliosides to sequester A beta from fibril formation was al
so evaluated by electron microscopy.