Solid-state NMR sequential assignment of Osaka-mutant amyloid-beta (Aβ1-40 E22Δ) fibrils.

Alzheimer's disease (AD) is the most common form of dementia. Aggregation of amyloid β (Aβ), a peptide of 39-43 residues length, into insoluble fibrils is considered to initiate the disease. Determination of the molecular structure of Aβ fibrils is technically challenging and is a significant goal in AD research that may lead to design of effective therapeutical inhibitors of Aβ aggregation. Here, we present chemical-shift assignments for fibrils formed by highly pure recombinant Aβ1-40 with the Osaka E22Δ mutation that is found in familial AD. We show that that all regions of the peptide are rigid, including the N-terminal part often believed to be flexible in Aβ wt.