Comparative properties of Aβ1-42, Aβ11-42, and [Pyr11]Aβ11-42 generated from O-acyl isopeptides

The use of water-soluble O-acyl isopeptides enabled us to investigate the biochemical properties of Aβ11-42 species, by preparing highly concentrated stock solutions after a pretreatment. Aβ11-42 and [Pyr11]Aβ11-42 showed comparable aggregation capability and cytotoxicity, suggesting that the pyroglutamate modification at Glu11 does not have a crucial role in these events. However, given that Aβ11-42 is converted to [Pyr11]Aβ11-42 by a glutamyl cyclase in vivo, the potential aggregative and cytotoxic nature of [Pyr11]Aβ11-42 that was observed in the present study provides valuable insights into the pathological functions of pyroglutamate-modified Aβ species in Alzheimer's disease.