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Here, we report the first synthesis of quasi-stable trimer models of full-length Aβ40 with a toxic conformation using a 1,3,5-phenyltris-L-alanyl linker at position 34, 36, or 38. The only trimer to exhibit weak neurotoxicity against SH-SY5Y cells was the one which was linked at position 38. This suggests that such a propeller-type trimer model is not prone to forming oligomers with potent neurotoxicity, which is in contrast with its corresponding dimer model.

Graphical abstract: Synthesis and biochemical characterization of quasi-stable trimer models of full-length amyloid β40 with a toxic conformation

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