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Background and purpose As a molecular chaperone, acetylcholinesterase ( ACh E; EC 3.1.1.7) plays a critical role in the pathogenesis of Alzheimer's disease ( AD). The peripheral anionic site ( PAS) of ACh E has been indicated as the amyloid-β (Aβ) binding domain. The goal of this study was to determine other motifs in ACh E involved in Aβ aggregation and deposition. Methods and results The β-hairpin in monomeric Aβ is the key motif of nucleation-dependent Aβ self-aggregation. As ACh E could induce Aβ aggregation and deposition, we searched ACh E for β-hairpin structures. In A11-specific dot blot assay, ACh E was detected by an oligomer-specific antibody A11, implying the existence of β-hairpin structures in ACh E as β-hairpin was the core motif of oligomers. A molecular superimposing approach further revealed that the N-terminal region, from Glu7 to Ile20, in ACh E ( ACh E 7-20) was similar to the β-hairpin domain in Aβ. The results of further dot blot assays, thioflavin T fluorescence assays, and electron microscopy imaging experiments, indicated that the N-terminal synthetic peptide ACh E7-20 had nearly the same ability as ACh E with regard to triggering Aβ aggregation and deposition. Conclusions ACh E 7-20, a β-hairpin region in ACh E, might be a new motif in ACh E capable of triggering Aβ aggregation and deposition. This finding will be helpful to design new and more effective Aβ aggregation inhibitors for AD treatment. [ABSTRACT FROM AUTHOR]