Introduction: Amyloid plaques, mainly comprising of amyloid-beta peptides derived from its precursor protein, are found deposited in hippocampal and entorhinal cortical regions of patients with Alzheimer’s disease (AD). However, none led to a complete understanding of the molecular mechanisms of the AD in order to generate a new therapy that would eradicate the disease effectively. Activation of pro-apoptotic pathway was found to be associated with the accumulation of amyloid precursor protein (APP). The objective of this study is to examine theeffects of APP overexpression on the Bcl-2 family proteins involving in pro-apoptotic pathway in neuronal cells. Methods: The experiment was first performed with the transfection of HEK 293T cells for generation of lentiviral vector system consisting APP plasmid followed by transduction of SH-SY5Y neuronal cells using lentivirus generated. Subsequently, western blot analysis was conducted to validate the APP overexpression in SH-SY5Y cells. Then, expression levels of Bcl-2 family proteins in the APP overexpressed cells were determined by western blot analysis. The statistical analysis was performed by Microsoft Excel with Student’s t-test. Results: APP overexpression in SH-SY5Y cells slightly upregulated the pro-apoptotic proteins including Bad, Bid, Bok and Puma but slightly downregulated Bcl-2, Bim and Bax. Conclusion: Our data suggest that APP overexpression regulated the Bcl-2-mediated pathway by a significant downregulation of Bim protein in neuronal cells.