NMR studies in aqueous solution fail to identify significant conformational differences between the monomeric forms of two Alzheimer peptides with widely different plaque-competence, A beta(1-40)(ox) and A beta(1-42)(ox)

NMR studies of amyloid beta -peptides (A beta) in aqueous solution provide a novel way in which to characterize the apparent Alzheimer's disease-relat ed conformational polymorphism of A beta. In the aqueous medium, neither of the polypeptides A beta (1-40)(ox) or A beta (1-42)(ox) (both of which con tain a methionine sulfoxide at position 35) is folded into a globular struc ture, but they both deviate from random coil behavior by local conformation al preferences of several short segments along the amino-acid sequence. Dif ferences between the solution structures of A beta (1-40)(ox) and A beta (1 -42)(ox) are indicated only by decreased flexibility of the region from abo ut residue 32 to the C-terminus in A beta (1-42)(ox) when compared to A bet a (1-40)(ox). The lack of the observation of more extensive conformational differences between the two molecules is intriguing, considering that A bet a (1-42)(ox) in aqueous solution has much higher plaque-competence than A b eta (1-40)(ox).