N-Terminally Truncated Amyloid-β(11-40/42) Cofibrillizes with its Full-Length Counterpart: Implications for Alzheimer's Disease

Abstract

Amyloid-β peptide (Aβ) isoforms of different lengths and aggregation propensities coexist in vivo. These different isoforms are able to nucleate or frustrate the assembly of each other. N-terminally truncated Aβ_(11-40) and Aβ_(11-42) make up one fifth of plaque load yet nothing is known about their interaction with full-length Aβ_(1-40/42) . We show that in contrast to C-terminally truncated isoforms, which do not co-fibrillize, deletions of ten residues from the N terminus of Aβ have little impact on its ability to co-fibrillize with the full-length counterpart. As a consequence, N-terminally truncated Aβ will accelerate fiber formation and co-assemble into short rod-shaped fibers with its full-length Aβ counterpart. This has implications for the assembly kinetics, morphology, and toxicity of all Aβ isoforms.

Keywords: Aβ peptides; aggregation; amyloid fibrils; co-assembly; protein folding.