Cholinesterase Inhibitor Reveals Synergistic Potential for Neural Stem Cell-Based Therapy in the 5xFAD Mouse Model of Alzheimer's Disease.

Background and objectives: Stem cell therapy shows great promise for treating Alzheimer's disease (AD). Cholinesterase inhibitors (ChEIs) like donepezil are well-established for alleviating AD symptoms. This study aimed to determine if combining ChEI treatment with stem cell therapy could improve therapeutic outcomes.

Methods: Neural stem cells (NSCs) were injected into the hippocampus of the 5xFAD AD mice using a stereotactic technique. Following this, donepezil or a placebo was administered for one month. We assessed behavioral improvements, survival and health of the grafts, and changes in synaptic density.

Results: The AD mice demonstrated cognitive impairment in both the Morris water maze and novel object recognition tests. In groups receiving stem cell therapy, donepezil enhanced the survival and neuronal differentiation of grafted NSCs, promoting the establishment of synaptic connections with the host brain. The combined treatment with donepezil and NSC transplantation more effectively increased synaptic density and improved behavioral performance in AD mice compared to NSC transplantation alone.

Conclusion: Combining ChEIs with NSC transplantation produces synergistic effects in AD treatment. This approach highlights the potential of integrating these therapies to develop more effective strategies for managing Alzheimer's disease.