Structure‐dependent effects of amyloid‐β on long‐term memory in Lymnaea stagnalis

Amyloid-β (Aβ) peptides are implicated in the causation of memory loss, neuronal impairment, and neurodegeneration in Alzheimer's disease. Our recent work revealed that Aβ 1–42 and Aβ 25–35 inhibit long-term memory (LTM) recall in Lymnaea stagnalis (pond snail) in the absence of cell death. Here, we report the characterization of the active species prepared under different conditions, describe which Aβ species is present in brain tissue during the behavioral recall time point and relate the sequence and structure of the oligomeric species to the resulting neuronal properties and effect on LTM. Our results suggest that oligomers are the key toxic Aβ1–42 structures, which likely affect LTM through synaptic plasticity pathways, and that Aβ 1–42 and Aβ 25–35 cannot be used as interchangeable peptides.