Background: Preclinical studies showed thatmesenchymal stem cells (MSCs) ameliorate tau phosphorylation, amyloid-betaaccumulation, and inflammation in Alzheimer’s disease (AD) mouse models viasecretion of neurotrophic factors and cytokines. We aimed to identify CSFbiomarkers that can be used to predict or monitor the response to MSCs inpatients with AD. Methods: AD patients were injected withhuman umbilical cord blood-MSCs (n=22) or placebo (n=12). The cerebrospinalfluid (CSF) samples were collected at baseline, one day after the firstinjection, and one day after the third injection. The patients injected withMSCs were classified into good responder (GR) or poor responder (PR) groupsbased on the rate of changes in the ratio of total-tau and phosphorylated-tauin the CSF. We selected three typical participants in each group, and their CSFprotein levels were analyzed using liquid chromatography-tandem massspectrometry (LC-MS/MS). Results: In the LC-MS/MS analysis 1,667proteins were identified. 11 proteins showed significant differences betweenthe typical GR and PR at baseline. Based on their significance level and knownfunctions two proteins, reticulocalbin-3 (RCN3) and follistatin-related protein3 (FSTL3), were selected as potential biomarkers to predict MSC response. 173proteins showed significant change one day after the third injection comparedto the baseline in typical GR. We excluded 45 proteins that showed significantchange after the third injection compared to the baseline in the typical PR.Based on their significance level and known function, four proteins,scrapie-responsive protein 1 (SCRG1), neural proliferation and differentiationcontrol protein (NPDC1), apolipoprotein E (ApoE), and cystatin C (CysC), wereselected as potential biomarker to monitor MSC response. Additionally,functional analysis revealed that the increased CSF proteins after the thirdinjection compared to the baseline in the typical GR were associated withsynaptogenesis. Conclusions: This study identified twoproteins (RCN3 and FSTL3) that may be potential biomarkers for predicting MSCresponse and four proteins (SCRG1, NPDC1, ApoE, CysC) that may be potentialbiomarkers for monitoring MSC response in patients with AD. Further studies areneeded to validate our results.