Abstract: Objective To assess the effect of the β-amyloid fragment Aβ_25-35 on mitochondria membrane potential and the concentration of intracellular calcium ion in primary hippocampal neurons.Methods Primary hippocampal neurons on the 8th day in vitro were treated with Aβ_25-35 at the concentration of 1 μmol/L,10 μmol/L,and 20 μmol/L for 24 hr,48 hr,and 72 hr with double distilled water as control.Purity of primary hippocampal neurons was determined on the eighth day after plating.The morphology of primary hippocampal neurons was determined by light microscope and electron microscopical.Ca²⁺_i and mitochondrial membrane potential were also determined.Results The results showed that Aβ_25-35 damaged the morphology and mitochondria function of primary hippocampal neurons.For 20 μmol/L Aβ_25-35 treatment group,the concentration of Ca²⁺ at 24,48,and 72 hr was 30.79±1.28,38.19±2.13,and 41.65±3.60,significantly higher than that of the control group and the mitochondrial membrane potential was 46.94±9.55,39.98±6.51,and 34.52±5.67,respectively,significantly lower than that of the control group.The results indicated that Aβ_25-35 decreased mitochondrial membrane potential and increasedCa²⁺_i in a dose-time dependent manner.Conclusion Aβ_25-35 exhibits a neurotoxicity effect by interfering the calcium homeostasis and disturbing the function of mitochondrial.