The objective is to evaluate the possible mechanisms of action of a water soluble curcumin derivative and MSCs in Alzheimer disease (AD). Materials and Methods: This work included: Seventy rats which were divided equally into: control group, AD group (induced by lipopolysaccharide), AD group received a novel curcumin derivative (NCD), AD group received pure curcumin, AD group received MSCs then NCD, AD group received MSCs, AD group received MSCs with NCD. Histopathological examination and gene expression of Bax, bcl2 and Seladin-1 gene expression in brain tissue and estimation of MDA and GSH in brain tissue by colorimetry were performed. Results: Histopathological examination of brain tissue from AD animals revealed the presence of plaques. Administration of MSCs or MSCs with NCD into rats after induction of experimental AD improved the histopathological picture with plaque disappearance and improved the behavior study, while other groups showed decrease of plaque formation. Gene expression demonstrated that bcl2 and Seladin-1 were upregulated while Bax gene was downregulated in all treated groups with a significant effect in the group treated with MSCs alone and group treated with both MSCs and NCD. MDA levels were decreased while GSH levels were increased in all treated groups. Conclusion: Administration of BM-derived MSCs either alone or with the NCD exerts a therapeutic effect on the brain lesion in Alzheimer's disease. This effect may be through the antioxidant and antiapoptotic action of both MSCs and curcumin. These data suggests that MSCs and curcumin may be a therapeutic target in treatment of AD.