Adipose Tissue-Derived Mesenchymal Stem Cells Alter Metabolites of Brain Cholesterol Homeostasis in An Alzheimer’s Model

Objective: Disruption of cholesterol homeostasis in Alzheimer’s disease (AD) plays a crucial role in diseasepathogenesis, making it a potential therapeutic target. Mesenchymal stem cells (MSCs) show promise in treatingcognitive impairment and provide a novel therapeutic approach. This study aims to investigate the effects of MSCs onspecific metabolites associated with brain cholesterol homeostasis in an AD rat model.Materials and Methods: In this experimental study, animals were divided into three groups: control, AD, andAD+MSCs. AD was induced using amyloid beta (Aβ) and confirmed through the Morris water maze (MWM) behaviouraltest and Congo red staining. MSCs were extracted, characterised via flow cytometry, subjected to osteoblast andadipose differentiation, and injected intraventricularly. The cholesterol metabolite levels were measured using gaschromatography-mass spectrometry (GC)-MS and compared among the groups.Results: Treatment with MSCs significantly improved memory function in the AD+MSCs group compared to theAD group and the number of beta-amyloid plaques decreased according to histological assessment. Disturbancesin the brain cholesterol metabolites that included desmosterol, 7-dehydrocholesterol, 24S-hydroxycholesterol,27-hydroxycholesterol and cholesterol were observed in the AD group compared to the control group. Treatment withMSCs resulted in significant alterations in the levels of these metabolites.Conclusion: The findings indicate that MSC therapy has the potential to improve AD by modulating brain cholesterolhomeostasis and promoting the differentiation of stem cells into nerve cells. The results emphasize the importance ofinvestigating the role of cholesterol metabolites in the context of MSC therapy to gain deeper insights into underlyingmechanisms of the therapeutic efficacy of MSCs in AD.