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Guanghui Jiang,* Cuicui Sheng,* Luxia Yan,* Zipeng Wang, Qing Wang, Rui Chen, Ying Zhao Department of Neurology, The Affiliated Huai’an Hospital of Xuzhou Medical University, Huai’an, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ying Zhao; Rui Chen, Email zhaoying772023@163.com; chenrui5980@163.comPurpose: To explore the relationship between the serum level of S100 calcium-binding protein, beta chain (S100β) and Parkinson’s disease (PD) with depression.Patients and Methods: A total of 145 patients with PD and 60 healthy controls matched for sex, age, and years of education in our hospital were selected. Fluorescence quantitative immunochromatography was used to quantify the level of S100β in serum. Clinical manifestations were assessed by Unified Parkinson’s Disease Rating Scale part-III (UPDRS-III), Hoehn & Yahr (H-Y) stage and 17-item Hamilton Rating Scale for Depression (HAMD-17). According to the results of HAMD-17, PD patients were divided into PD with depression group and PD without depression group. The relationship between serum S100β and HAMD-17 scores in PD patients with depression was investigated through correlation analysis and multivariate regression analysis, and receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of serum S100β.Results: The level of serum S100β in PD with depression group was significantly higher than that in PD without depression group and control group. In PD patients with depression, serum S100β level was positively correlated with UPDRS-III score, H-Y Scale and HAMD-17 score. The HAMD-17 score was positively correlated with the UPDRS-III and H-Y scales, and the increase in the HAMD-17 score was associated with women. Elevated serum S100β level and UPDRS-III score are independent risk factors for PD with depression. Analysis of receiver operating characteristic (ROC) curves showed that the serum S100