中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (5): 885-892.doi: 10.4103/1673-5374.297091

• 原著:退行性病与再生 • 上一篇    下一篇

胶质细胞源性神经营养因子预测帕金森病患者的认知障碍可能性

  

  • 出版日期:2021-05-15 发布日期:2020-12-29
  • 基金资助:
    国家自然科学基金(81971006);江苏省研究生科研与实践创新计划(KYCX18U 2193,KYCX18 U 2171)。

Possible role of glial cell line-derived neurotrophic factor for predicting cognitive impairment in Parkinson’s disease: a case-control study

Ming-Yu Shi1, 2, #, Cheng-Cheng Ma3, #, Fang-Fang Chen4, Xiao-Yu Zhou1, Xue Li5, Chuan-Xi Tang3, Lin Zhang3, Dian-Shuai Gao3, *#br#   

  1. 1 Department of Neurology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China;  2 Department of Neurology, the First People’s Hospital of Yancheng, Yancheng, Jiangsu Province, China;  3 Department of Neurobiology and Anatomy, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou, Jiangsu Province, China;  4 Department of Neurology, Suqian First People’s Hospital, Suqian, Jiangsu Province, China;  5 Department of Operating Room, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China
  • Online:2021-05-15 Published:2020-12-29
  • Contact: Dian-Shuai Gao, PhD, gds@xzhmu.edu.cn.
  • Supported by:
    This work was funded by the National Natural Science Foundation of China, No. 81971006 (to DSG); the Postgraduate Research and Practice Innovation Program of Jiangsu Province of China, Nos. KYCX18_2193 (to MYS), KYCX18_2171 (to CXT). 

摘要:

胶质细胞系源性神经营养因子(GDNF)在多巴胺能神经元保护中起着重要作用,但鲜有关于GDNF与帕金森病患者认知功能障碍之间关系的报道。为明确帕金森病患者血清GDNF、GDNF前体(α-pro-GDNF、β-pro-GDNF)水平与帕金森病患者认知功能障碍之间的关系,并探究其作为诊断标记物的可能性。试验纳入来自徐州医科大学附属医院门诊及住院的帕金森病患者53例(男23例,女30例),平均年龄66.58岁,根据认知障碍量表简易精神状态量表、蒙特利尔认知评估量表、临床痴呆评定量表评分将患者分成帕金森病患者认知功能障碍组27例和帕金森病不伴认知功能障碍组26例。另纳入26名性别、年龄匹配的健康老年人作为对照组。结果显示,(1)帕金森病患者不伴认知功能障碍组血清GDNF水平显著高于健康对照组和帕金森病患者认知功能障碍组,各组GDNF前体(α-pro-GDNF、β-pro-GDNF)水平无显著差异;(2)相关性分析结果显示,血清GDNF水平、GDNF/α-pro-GDNF、GDNF/β-pro-GDNF与3个量表评分呈中度以上的相关性;(3)进一步采用Logistic回归分析和逐步线性回归分析寻找帕金森病患者认知功能障碍的危险因素,发现GDNF和Hoehn-Yahr分期是帕金森病患者认知功能障碍的危险因素,也是3种认知障碍量表评分的共同影响因素;GDNF前体(α-pro-GDNF、β-pro-GDNF)不是帕金森病认知功能障碍的危险因素;(4)试验绘制了血清GDNF预测帕金森病患者认知功能状态模型的ROC曲线显示,曲线下面积为0.859,即血清GDNF正确区分帕金森病患者有无认知功能障碍的可能性为0.859;(5)上述数据证实,血清GDNF可有效地预测帕金森病患者认知功能障碍;而GDNF前体(α-pro-GDNF、β-pro-GDNF)不能预测帕金森病患者认知功能状态。

https://orcid.org/0000-0001-8567-0238 (Dian-Shuai Gao)

关键词:

因子, GDNF, 生物标记物, 认知, 神经元, 神经退行性疾病, 帕金森病, 危险因素

Abstract: Glial cell line-derived neurotrophic factor (GDNF) plays an important role in the protection of dopaminergic neurons, but there are few reports of the relationship between GDNF and its precursors (α-pro-GDNF and β-pro-GDNF) and cognitive impairment in Parkinson’s disease. This study aimed to investigate the relationship between the serum levels of GDNF and its precursors and cognitive impairment in Parkinson’s disease, and to assess their potential as a diagnostic marker. Fifty-three primary outpatients and hospitalized patients with Parkinson’s disease (23 men and 30 women) with an average age of 66.58 years were enrolled from the Affiliated Hospital of Xuzhou Medical University of China in this case-control study. The patients were divided into the Parkinson’s disease with cognitive impairment group (n = 27) and the Parkinson’s disease with normal cognitive function group (n = 26) based on their Mini-Mental State Examination, Montreal Cognitive Assessment, and Clinical Dementia Rating scores. In addition, 26 age- and sex-matched healthy subjects were included as the healthy control group. Results demonstrated that serum GDNF levels were significantly higher in the Parkinson’s disease with normal cognitive function group than in the other two groups. There were no significant differences in GDNF precursor levels among the three groups. Correlation analysis revealed that serum GDNF levels, GDNF/α-pro-GDNF ratios, and GDNF/β-pro-GDNF ratios were moderately or highly correlated with the Mini-Mental State Examination, Montreal Cognitive Assessment, and Clinical Dementia Rating scores. To explore the risk factors for cognitive impairment in patients with Parkinson’s disease, logistic regression analysis and stepwise linear regression analysis were performed. Both GDNF levels and Hoehn-Yahr stage were risk factors for cognitive impairment in Parkinson’s disease, and were the common influencing factors for cognitive scale scores. Neither α-pro-GDNF nor β-pro-GDNF was risk factors for cognitive impairment in Parkinson’s disease. A receiver operating characteristic curve of GDNF was generated to predict cognitive function in Parkinson’s disease (area under the curve = 0.859). This result indicates that the possibility that serum GDNF can correctly distinguish whether patients with Parkinson’s disease have cognitive impairment is 0.859. Together, these results suggest that serum GDNF may be an effective diagnostic marker for cognitive impairment in Parkinson’s disease. However, α-pro-GDNF and β-pro-GDNF are not useful for predicting cognitive impairment in this disease. This study was approved by Ethics Committee of the Affiliated Hospital of Xuzhou Medical University, China (approval No. XYFY2017-KL047-01) on November 30, 2017. 

Key words: biomarkers, cognition, factors, GDNF, neurodegenerative diseases, neurons, Parkinson’s disease, risk factors