Objective To investigate the effect and mechanism of lncRNA NEAT1 activating PI3K/Akt signaling pathway on the influence of Alzheimer's disease (AD) PC12 model cells apoptosis induced by Aβ_25-35. Methods PC12 cells were induced with Aβ_25-35 of concentrations 0, 5, 10 and 20 μmol/L to construct AD cell model. PC12 cells were treated with 5 μmol/L Aβ_25-35, and the relative expression level of lncRNA NEAT1 was detected by qRT-PCR at the time points 24, 48 and 72 hours,respectively. PC12 cells were divided into: (1) control group, lncRNA NEAT1 knockdown group, si-NC group, empty body group and lncRNA NEAT1 overexpression group. Among them the cells in control group were not treated anyway; in the other four groups were cultured with Opti-MEM medium containing si-lncRNA NEAT1, si-NC, pcDNA3.1-NC and pcDNA3.1-lncRNA NEAT1 and transfected for 8 hours, and then treated with 20 μmol/L Aβ_25-35; qRT-PCR was used to detect the relative expression level of lncRNA NEAT1; CCK-8 was used to detect the cell viability; flow cytometry was used to detect the apoptosis of PC12 cells, and the proliferation of PC12 cells was reflected by the ratio of G₁ to G₂ phase of cell cycle; the inflammatory factors interleukin-1β (IL-1β),IL-6, IL-18, and tumor necrosis factor-α (TNF-α) in cell supernatant were detected by ELISA. (2) control group, empty body group,and lncRNA NEAT1 overexpression group, Western blotting was used to detect the relative expression levels of p-PI3K and p-Akt.(3) control group, si-NC group, lncRNA NEAT1 knockdown group, empty body group, lncRNA NEAT1 overexpression group, and lncRNA NEAT1 overexpression+LY294002 group. Cells in lncRNA NEAT1 overexpression+LY294002 group were transfected with pcDNA3.1-lncRNA NEAT1, and 10 μmol/L P13K pathway inhibitor LY294002 were added, and then flow cytometry was used to detect the apoptosis of PC12 cells. Results Different concentrations of Aβ_25-35 could significantly inhibit the expression of lncRNA NEAT1 in a concentration-dependent manner (P=0.001). Compared with empty body group, the relative expression level of lncRNA NEAT1, the cell proliferation rate, and the proportion of cells in G₂ phase of lncRNA NEAT1 overexpression group increased, the cell apoptosis rate and the proportion of cells in G₁ phase decreased (P<0.05). Compared with si-NC group, the relative expression level of lncRNA NEAT1, the cell proliferation rate, and the proportion of cells in G₂ phase of lncRNA NEAT1 knockdown group decreased, the cell apoptosis rate and the proportion of cells in G₁ phase increased (P<0.05). ELISA results showed that, compared with empty body group, the levels of inflammatory factors IL-1β, IL-6, IL-18, and TNF-α decreased significantly in lncRNA NEAT1 overexpression group (P<0.05); compared with si-NC group, the levels of inflammatory factors IL-1β, IL-6, IL-18 and TNF-α increased significantly in lncRNA NEAT1 knockdown group (P<0.05). Western blotting results showed that, compared with empty body group, the expression levels of signal pathway related proteins p-PI3K and p-Akt increased in lncRNA NEAT1 overexpression group (p-PI3K: 0.86±0.05 vs. 0.15±0.02, P=0.003; p-Akt: 0.86±0.06 vs. 0.11±0.04, P=0.000). Compared with lncRNA NEAT1 overexpression group, the apoptosis rate in lncRNA NEAT1 overexpression+LY294002 group increased obviously (9.00%±0.10%vs. 5.13%±0.21%, P=0.004). Conclusion lncRNA NEAT1 can promote Aβ_25-35 induced PC12 cell proliferation and inhibit cell apoptosis by regulating PI3K/Akt pathway.