Solid State NMR of Fibrillar Beta Amyloid Isoforms

Abstract

The 40-43 residue-long beta amyloid peptides aggregate in the extracellular neuronal space to form amyloid plaques, which contain numerous beta amyloid fibrils. Biological interest in amyloid fibrils arises from their occurrence in amyloid diseases, such as Alzheimer's disease (AD). The truncated pyroglutamate beta amyloid (p3-42) and beta amyloid (4-42) peptides are two of the most dominant isoforms found in excised amyloid material from AD brains. We investigate the self-seeding and cross-seeding behavior of the different amyloid beta isoforms, and utilize magic angle spinning NMR techniques to study the molecular structure of the fibrils formed by the amyloid beta (p3-42) and (4-42) peptides. The structures of these fibrils are compared to the available structures of the wild type and mutant beta amyloid (1-40) and (1-42) fibrils.