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

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.