Introduction: The aging process is the most significant risk factor for developing Alzheimer’s disease (AD). AD is the most common neurodegenerative disease that causes cognitive and memory impairment in the elderly. Excessive build-up of amyloid protein leads to cell death, brain atrophy, and cognitive and functional decline in AD. The nuclear factor kappa beta (NF-κB) is a family of inducible transcription factors composed of NF-κB1, NF-κB2, RelA, RelB and c-Rel. It is activated by genotoxic agents, as well as oxidative and inflammatory stresses. It regulates expression of genes that control apoptosis, cell cycle progression, cell senescence, and inflammation. NF-κB regulates amyloid precursor protein (APP) processing by activating transcription of β and γ secretases, which promotes amyloid dysregulation in AD. In addition, NF-κB activation is linked with many of the known lifespan regulators including insulin/IGF- 1, FOXO, SIRT, and mTOR. Therefore, NF-κB pathway contributes to the pathophysiology of AD. This study aims to evaluate the effects of APP overexpression on NF-κB pathway in neuronal cells. Methods: SH-SY5Y neuronal cells were transduced with APP plasmid. Overexpression of APP in the cells was validated by western blotting. Western blot analysis using antibodies targeting NF-κB signalling pathway was performed using the APP-overexpressed cells. Results: Overexpression of APP in cells caused a significant down-regulation of phosphorylated NF-κB. Overexpression of APP also slightly up-regulated IkappaB-alpha, IKK alpha, and IKK beta. Conclusion: APP overexpression affected NF-κB pathway by down-regulating NF-κB protein.