Quenched hydrogen-deuterium exchange NMR of a disease-relevant Aß(1-42) amyloid polymorph

Abstract

Alzheimer's disease is associated with the aggregation into amyloid fibrils of Aß(1±42) and Aß(1±40) peptides. Interestingly, these fibrils often do not obtain one single structure but rather show different morphologies, so-called polymorphs. Here, we compare quenched hydrogen-deuterium (H/D) exchange of a disease-relevant Aß(1±42) fibril for which the 3D structure has been determined by solid-state NMR with H/D exchange previously determined on another structural polymorph. This comparison reveals secondary structural differences between the two polymorphs suggesting that the two polymorphisms can be classified as segmental polymorphs.