Comparison of Alzheimer Aβ(1-40) and Aβ(1-42) amyloid fibrils reveals similar protofilament structures

We performed mass-per-length (MPL) measurements and electron cryomicroscopy (cryo-EM) with 3D reconstruction on an A beta(1-42) amyloid fibril morphology formed under physiological pH conditions. The data show that the examined A beta(1-42) fibril morphology has only one protofilament, although two protofilaments were observed with a previously studied A beta(1-40) fibril. The latter fibril was resolved at 8 angstrom resolution showing pairs of beta-sheets at the cores of the two protofilaments making up a fibril. Detailed comparison of the A beta(1-42) and A beta(1-40) fibril structures reveals that they share an axial twofold symmetry and a similar protofilament structure. Furthermore, the MPL data indicate that the protofilaments of the examined A beta(1-40) and A beta(1-42) fibrils have the same number of A beta molecules per cross-beta repeat. Based on this data and the previously studied A beta(1-40) fibril structure, we describe a model for the arrangement of peptides within the A beta(1-42) fibril.