BACKGROUND: Many studies have indicated that amyloid beta-protein (Aβ) plays an important role in the pathophysiology of Alzheimer disease (AD), the reduction of production of Aβ can slow down the deterioration of AD, so to reduce Aβ production could become an important therapeutic target in AD. Many AD patients present behavioral disturbance and psychotic symptoms, and are treated with antipsychotics. Olanzapine and quetiapine can significantly improve the clinical global impressions(CGI) severity-of-Alzheimer scores, clinical studies suggest that early and prolonged intervention can improve long-term outcome.OBJECTIVE: To investigate the effect of olanzapine and quetiapine on the secretion of Aβ42 in Swedish amyloid precursor protein(APP) gene and presenilin 1 gene transfected murine N2a neuroblastoma cells.DESIGN: A completely randomized controlled trial based on N2a cells.MATERIALS: Setting was at Neuropsychiatry Research Institute of Medical College, University of Saskatchewan. The murine N2a and double transfected N2a cell was provided by department of neurology and neuroscience, Cornell university medical college.INTERVENTIONS: The double transfected murine N2a neuroblastoma cells were treated for 24 hours with 200 μmol/L olanzapine and 50 μ mol/L quetiapine respectively, then intracellular and extrocellular levels of Aβ were determined. The MTT assay was used to determine cell viability; the BCA assay was used to determine the protein content of cells; the western blot analysis was used to determine the APP expression; and the Enzyme-Linked-Immuno-Sorbent Assay(ELISA) was used to determine the Aβ produced by double transfected murine N2a neuroblastoma cells.MAIN OUTCOME MEASURES: The levels of intracellular and extracellullar Aβ 42 secreted by double transfected murine N2a neuroblastoma cells were detected using ELISA.RESULTS: The double transfected N2a cells produced more APPs than the naive N2a cells. The extracellular Aβ[ (4.78 ± 0.54) nmol/L] of cells treated with olanzapine decreased significantly comparing to the vehicle [(7.69±0.62) nmol/L] (t=3.52, P ＜0.05); and theextracellular Aβ[ (4. 09 ±0. 18) nmol/L] of cells treated with quetiapine decreased significantly comparing to the vehicle[ (7.50 ±0.50) nmol/L] ( t =5.61,P ＜ 0.05) . The intracellular Aβ of cells treated with olanzapine did not change significantly conpared with the vehicle ( P ＞ 0.05 ); the intracellular Aβ of cells treated with quetiapine did not change significantly compared with the vehicle ( P ＞ 0.05 ).CONCLUSION: The result suggests that olanzapine and quetiapine can decrease the production of Aβ42 in double transfected murine N2a neuroblastoma cells and clinically may be helpful in slowing down the progression of AD by decreasing the extrocellular secretion of Aβ42.