AbstractBackgroundStatistical analysis of myelin basic protein (MBP) cells generated from Neural progenitor cell (NPC)‐derived Oligodendrocyte precursor cells (OPCs) treated with various AChEIs, including donepezil, huperzine A, rivastigmine and tacrine, revealed that only donepezil is capable of facilitating OPC‐to‐OL formation, indicating that donepezil’s effect in promoting OPC differentiation is not dependent on the inhibition of AChE. So, it can be possible that OPC‐to‐OL formation is why donepezil is considered leading in Alzheimer’s disease (AD) treatment.MethodTrial will include transgenic rat line Tg6590 that expresses human APP with the Swedish mutation driven by the ubiquitin promoter that doesn’t develop extracellular beta‐amyloid pathology before 15 months at least. Controlling their genome influence, the cognitive characteristics of mice can be related to neurobiological characteristics only. Excluding a standard (S), group of control animals was subjected to a CPZ‐free diet; rat (+MBP) will be injected with OPCs, and rat (‐MBP) will be supplemented with 0.6% cuprizone (CPZ) for 2 weeks, which facilitates demyelination. This study enables us to observe the myelination effect on its behavioral impairment (n = 3). Luxol fast blue (LFB) test or MBP tracking will be held monthly to observe OPCs‐to‐OL process. It was reported that Tg6590 rats display learning and memory deficits in the Morris water maze at the age of 9 months and altered spontaneous behavior measured in open‐field. So, with continuous behavioral observations, by procedure for a redundant place/cued version of Morris water maze task, memory‐learning assessment (MLA) will depend upon duration it takes to observe obvious behavioral impairment.ResultThis clinical trial is now under process and it is set to start by late 2024.ConclusionOPCs implantation may lead to axonal adaptation to physical stress with less beta‐amyloid and may also maintain the myelination density in CNS, especially in hippocampal‐neocortical neural connections, which can be therapeutically efficient for memory‐learning deficits.