Increasing evidence has suggested that formation and propagation of misfolded aggregates of 42-residue human amyloid β (Aβ(1–42)), rather than of the more abundant Aβ(1–40), provokes the Alzheimer's disease cascade. However, structural details of misfolded Aβ(1–42) have remained elusive. Here we present the atomic model of an Aβ(1–42) amyloid fibril, from solid-state NMR (ssNMR) data. It displays triple parallel-β-sheet segments that differ from reported structures of Aβ(1–40) fibrils. Remarkably, Aβ(1–40) is incompatible with the triple-β-motif, because seeding with Aβ(1–42) fibrils does not promote conversion of monomeric Aβ(1–40) into fibrils via cross-replication. ssNMR experiments suggest that C-terminal Ala42, absent in Aβ(1–40), forms a salt bridge with Lys28 to create a self-recognition molecular switch that excludes Aβ(1–40). The results provide insight into the Aβ(1–42)-selective self-replicating amyloid-propagation machinery in early-stage Alzheimer's disease.