Abstract: Objective To study neurocognitive changes at different postoperative time points and the potential mechanisms in APP/PS1 transgenic mice (2xTg AD mice). Methods APP/PS1 mice were randomly divided into two groups, experiment group (received laparotomy under 2.5% sevoflurane anesthesia) and control group. Fear conditioning test was introduced to assess the cognitive function at 1d and 3ds after the anesthesia/surgery. The content of alpha-synuclein in hippocampus was determined by Western blot, while the contents of Aβ42, IL-6, IL-1beta, and TNF-alpha were quantified by ELISA kits at different postoperative time points (12h, 24h and 3d). Results Compared with the control group，the context-associated freezing duration was significantly decreased at 1d and 3ds after the Anesthesia/surgery; the concentration of IL-6,IL-1beta and TNF-alpha significantly increased at 24hs after the Anesthesia/surgery; the content of alpha-synuclein and Aβ42 also significantly increased at 24hs after the Anesthesia/surgery（P＜0.05）. Conclusion The anesthesia/surgery has effects on the short-term cognitive function of 2xTgAD mice. The potential mechanisms may be associated with the variation of alpha-synuclein and amyloid-β42, besides neuroinflammation.

Key words: APP/PS1 transgenic mice, postoperative neurocognitive disorders, alpha-synuclein