OBJECTIVE TO investigate the effect of high dose 0-amyloid 1-42 oligomers (AβO1-42) on adult hippocampal neural stem/progenitor cells (NSC) in vitro.METHODS NSC was treated with AβO1-42 (3-10 μmnol · L-1) for 5 d.Measurements of cell proliferation were performed using a bro modeoxyuridine (5-bromo-2-deoxyuridine, BrdU) incorporation assay.Intracellular reactive oxygen species (ROS) levels were monitored by using 2, 7-dichlorofluorescin diacetate (DCFH DA).NSC senescence was evaluated by using SA-0-gal (senes cence-associated β-galactosidase) assay.Antioxidant N-acetyl L-cysteine (NAC) and p38 inhibitor SB20358 were tested for their effects on the AβO1-42-induced NSC senescence.The ex pressions of p38 kinase phosphorylation and prosenescence mole cules pl6INK4a and Rb were determined by Western blotting.RESULTS High dose AβO1-42 dose-dependently inhibited NSC proliferation, and enhanced intracellular ROS levels, con tributing to NSC senescence (P <0.05).In addition, A0O1-42upregulated p38 kinase phosphorylation, pl6INK4a and Rb pro tein expression.Either 1 mmol· L-1 NAC or 10 μrnol· L-1SB203580 attenuated the levels of AβO1-42-enhanced p16INK4a and Rb protein expression, and prevented AβO1-42-induced NSC senescence.CONCLUSION High dose AβO1-42 induce NSC senescence via ROS-p38-p16-Rb pathway, thereby inhibiting a dult neurogenesis.