Targeting probes were used to track Aβ_25-35 subcellular localization,while Nrf2 signaling pathway were used to investigate the protective mechanism of Fomes officinais Ames polysaccharides components (FOAPs-a) and (FOAPs-b) against β-amyloid (Aβ_25-35)-induced mitochondrial damage pathways in PC12 cells.The PC12 cells were cultured and activated by Aβ_25-35 in condensed state as Alzheimer's disease cell model in vitro and were randomly divided into nine groups:control group、Aβ_25-35(40 μmol/L)induced group、Aβ_25-35+ FOAPs-a (50,100,200 μg/mL) groups and Aβ_25-35 + FOAPs-b (50,100,200 μg/mL) groups.Targeting probes were used to track Aβ_25-35 subcellular localization,The changes of the reactive oxygen species ( ROS) in PC12 cells were detected by the kit.The expression of apoptosis-related proteins Bax and Bcl2 and the expression of Nrf2、ASK1 and phosphorylated ASK1 proteins related to the Nrf2-pathway were analyzed by Western boltting method.It was found that after stimulated by Aβ_25-35,the cells mitochondrial integrity were changed,after the addition of 200 μg/mL FOAPs-a or b pretreated PC12 cells,it can significantly alleviate the mitochondria damage by Aβ_25-35,while reducing the co-localization of mitochondria.FOAPs-a and FOAPs-b could significantly inhibit the accumulation of ROS induced by Aβ_25-35 in PC12 cells in a dose-dependent manner.They could also effectively prevent Aβ_25-35-stimulated cytotoxicity,which involved in attenuating cell apoptosis,increasing Nrf2 expression and the ratio of Bcl-2/Bax,as well as inhibiting ASK1 and phosphorylated ASK1 proteins levels.In conclusion FOAPs-a and FOAPs-b played neuroprotective roles against Aβ_25-35-induced cytotoxicity in PC12 cells through suppressing the mitochondria-mediated apoptotic pathway.The mechanism may be related to its suppression of the activation of Nrf2 signal pathway.