The study investigates the structural conversion of neurotoxic amyloid-β(1–42) oligomers to fibrils, a process crucial for understanding Alzheimer's disease (AD). Low temperature and low salt conditions stabilize disc-shaped pentamers of Aβ42, which are more toxic to murine cortical neurons than protofibrils and fibrils. These neurotoxic oligomers lack the characteristic β-sheet structure of fibrils and are composed of loosely aggregated strands with a turn conformation. NMR spectroscopy reveals that the structural conversion involves the association of these strands into β-sheets, with individual β-strands polymerizing in a parallel, in-register orientation and staggered at an inter-monomer contact between Gln15 and Gly37. The study also highlights the importance of the Phe19-Leu34 packing in both oligomers and fibrils, and the staggered conformation of β-strands in fibrils. The findings provide insights into the toxicity and aggregation properties of Aβ42, which are key to developing therapeutic and diagnostic strategies for AD.The study investigates the structural conversion of neurotoxic amyloid-β(1–42) oligomers to fibrils, a process crucial for understanding Alzheimer's disease (AD). Low temperature and low salt conditions stabilize disc-shaped pentamers of Aβ42, which are more toxic to murine cortical neurons than protofibrils and fibrils. These neurotoxic oligomers lack the characteristic β-sheet structure of fibrils and are composed of loosely aggregated strands with a turn conformation. NMR spectroscopy reveals that the structural conversion involves the association of these strands into β-sheets, with individual β-strands polymerizing in a parallel, in-register orientation and staggered at an inter-monomer contact between Gln15 and Gly37. The study also highlights the importance of the Phe19-Leu34 packing in both oligomers and fibrils, and the staggered conformation of β-strands in fibrils. The findings provide insights into the toxicity and aggregation properties of Aβ42, which are key to developing therapeutic and diagnostic strategies for AD.