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

Abstract

NMR studies of amyloid β-peptides (Aβ) in aqueous solution provide a novel way in which to characterize the apparent Alzheimer's disease-related conformational polymorphism of Aβ. In the aqueous medium, neither of the polypeptides Aβ(1-40)ox or Aβ(1-42)ox (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 Aβ(1-40)ox and Aβ(1-42)ox are indicated only by decreased flexibility of the region from about residue 32 to the C-terminus in Aβ(1-42)ox when compared to Aβ(1-40)ox. The lack of the observation of more extensive conformational differences between the two molecules is intriguing, considering that Aβ(1-42)ox in aqueous solution has much higher plaque-competence than Aβ(1-40)ox.