To observe the effect of tenuigenin (TEN) on aggregated amyloid beta-protein 1-40 (Abeta(1-40)-induced cytotoxicity of primary cultural cortical neurons in vitro.In order to establish neurotoxic model, the primary cultural rat cortical neurons were treated with 25 micromol x L(-1) aggregated Abeta(1-40), which were divided into a model group and 3 different dose groups of TEN (50, 100, 200 micromol x L(-1), respectively), and a normal control group with no treatment of Abeta(1-40) was set up. The morphological changes of the neurons before and after administration of TEN were examined under a phase contrast microscope. Neuronal viabilities were detected by MTT colorimetry. Injuring degrees of the neuronal membrane were assessed by lactate dehydrogenase (LDH) colorimetry.As compared with the normal control, treatment of primary cultural neurons with Ap, (25 micromol x L(-1)) for 24 h caused a significant decrease in viabilities and morphological changes of nerve cells, with neurons losing adherent ability or shedding, and the synapse shortening found by microscope. The percentage of apoptotic nerve cells and the LDH leakage were significantly decreased, and the survival rate of neurons was significantly increased in both the TEN high and medium dose groups.The aggregated Abeta(1-40) has a definite neurotoxicity for cultural cortical neurons, and TEN can significantly protect the neurons from the cytotoxicity of Abeta(1-40).