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

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