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

NMR studies of amyloid b-peptides (Ab) in aqueous solution provide a novel way in which to characterize the apparent Alzheimer’s disease-related conformational polymorphism of Ab. In the aqueous medium, neither of the polypeptides Ab(1–40) or Ab(1–42) (both of which contain a methionine sulfoxide at position 35) is folded into a globular structure, but they both deviate from random coil behavior by local conformational preferences of several short segments along the amino-acid sequence. Differences between the solution structures of Ab(1–40) and Ab(1–42) are indicated only by decreased flexibility of the region from about residue 32 to the C-terminus in Ab(1–42) when compared to Ab(1–40). The lack of the observation of more extensive conformational differences between the two molecules is intriguing, considering that Ab(1–42) in aqueous solution has much higher plaquecompetence than Ab(1–40).