Infusion of neural precursors improves memory impairment in mouse models of Alzheimer’s disease

Background Currently available treatments for Alzheimer’s disease (AD) are essentially symptomatic and not disease‐modifying, positioning it as a serious global health problem with the increase of the elderly population. This disease is clinically characterized by progressive memory impairment and cognitive dysfunction. The neuropathological hallmarks of AD are the accumulation of extracellular β‐amyloid (Aβ) peptide in senile plaques, intracellular deposition of hyper‐phosphorylated tau as neurofibrillary tangles (TNF), neurodegeneration, synaptic loss throughout the brain, and a neuroinflammatory process governed by the activation of glial cells. Recently, stem cell therapy has provided great potential in treating AD patients. However, there is an urgent need to replace the conventional intracerebral stem cell therapy for a less invasive method to avoid some of the technical challenges. Our recently published results indicated that peripheral treatment with neural precursors (NPs) ameliorates clinical symptoms by reducing the disease‐associated neuroinflammation in a mouse model of Parkinson’s disease. Therefore, we hypothesize that intravenous administration of NPs and their released neurotrophic factors can be used as a non‐invasive therapy to ameliorate memory impairment in mouse models of AD. Method In this pre‐clinical study, NPs derived from mesenchymal stem cells (MSC‐NPs) and induced pluripotent stem cells (iPSC‐NPs) were intravenously injected into APP/PS1 and P301S mice at 3 and 6 months old (before and after brain pathology is established). Before treatment and at the age of 7 months old, experimental and control (PBS) animals were subjected to Barnes maze task, novel object recognition and rotarod test. Result NPs treated mice displayed an amelioration in memory dysfunction compare to the PBS‐injected animals. In addition, P301S mice injected with NPs showed improved motor function to rotarod coordination test in comparison to the control group. Conclusion Peripheral inoculation using NPs could be used as a treatment to reduce AD‐related clinical signs.