[Introduction] It is widely known that patients with Alzheimer’s disease (AD) often present depression, which is one of the risk factors for developing AD. Although antidepressants have been used in many patients with AD, the evidence of their cognitive benefit remains inconsistent. AD is characterized pathologically by amyloid-βpeptide (Aβ) deposition and neurofibrillary tangles in brain. In this study, we evaluated if treatment with antidepressants could modulate neuronal damage induced by the highly toxic Aβ oligomers (Aβo). 
[Methods] Aβ_1-42 aggregation was measured using thioflavin T. We prepared 5 μM Aβo solution using Aβ_1-42peptides and induced neuronal toxicity in SH-SY5Y cells (human neuroblastoma) using Aβo. SH-SY5Y cells were treated with duloxetine (Dlx), venlafaxine (Ven), mirtazapine(Mir) and fluoxetine(Flx) and Aβo. Cell viability and oxidative stress were measured.
[Results] Dlx and Flx inhibited Aβ_1-42 aggregation in concentration-dependent manner. Dlx and Flx significantly reduced Aβo-induced cytotoxicity compared to Aβo-alone group after 24 hr of treatment. All four antidepressants reduced ROS production significantly in concentration-dependent manner compared to Aβ-o alone group after 30 min of treatment. 
[Conclusion] These results suggest that antidepressants, especially Dlx and Flx, may be effective in preventing and suppressing the progression of AD through multiple mechanisms such as inhibition of　Aβ aggregation and antioxidative effect.