Predictive Value and Mechanism of Plasma proBDNF, mBDNF, and t-PA Levels for Cognitive Impairment in Cerebral Small Vessel Disease

doi:10.3969/j.issn.1673-5765.2026.03.005

Abstract

Abstract: Objective To explore the predictive value and underlying mechanisms of plasma precursor of brain-derived neurotrophic factor (proBDNF), mature brain-derived neurotrophic factor (mBDNF), and tissue-type plasminogen activator (t-PA) levels for cognitive impairment in cerebral small vessel disease (CSVD).
Methods A cross-sectional case-control study was conducted to enroll CSVD patients admitted to the Department of Neurology, the Second Affiliated Hospital of Kunming Medical University from November 2021 to November 2022. The patients were classified into a CSVD with normal cognition group and a CSVD with cognitive impairment group based on their educational level and MoCA score. Meanwhile, eligible healthy volunteers receiving physical examination, as well as family members and caregivers of CSVD patients during the same period, were selected as the control group. Enzyme linked immunosorbent assay was used to detect plasma concentrations of proBDNF, mBDNF, and t-PA. The total CSVD burden was assessed by the total CSVD burden score (0-4 points), and cognitive function was evaluated by the MoCA. Analysis of covariance was performed to adjust for confounding factors and compare the differences in plasma biomarker levels among the three groups. Partial correlation analysis was applied to explore the correlations between plasma biomarker levels and MoCA scores. ROC curves were used to evaluate the discriminatory efficacy of plasma biomarker levels and the combined model in distinguishing CSVD with cognitive impairment from CSVD with normal cognition.
Results A total of 131 subjects were enrolled, including 32 in the control group, 38 in the CSVD with normal cognition group, and 61 in the CSVD with cognitive impairment group. After adjusting for confounding factors, plasma proBDNF level in the CSVD with cognitive impairment group was lower than that in the CSVD with normal cognition group and the control group, and plasma mBDNF level was lower than that in the control group, whereas plasma t-PA level was higher than that in the control group (all P<0.05). Partial correlation analysis showed that plasma proBDNF and mBDNF levels were positively correlated with total MoCA scores (r=0.439, P<0.001; r=0.269, P=0.007), while plasma t-PA level was negatively correlated with total MoCA scores (r=-0.270, P=0.007). ROC curve analysis indicated that plasma proBDNF and t-PA levels had moderate predictive value in distinguishing CSVD with cognitive impairment from CSVD with normal cognition (AUC 0.709, P<0.001; AUC 0.684, P<0.001). The combined model constructed based on plasma levels of proBDNF, mBDNF, and t-PA, and the total CSVD burden score had the optimal predictive efficacy (AUC 0.844, 95%CI 0.779-0.908).
Conclusions Reduced plasma proBDNF and mBDNF levels and elevated t-PA level were observed in CSVD patients with cognitive impairment, and the changes were associated with the severity of cognitive impairment. Plasma proBDNF and t-PA levels have moderate predictive value for cognitive impairment in CSVD, and the combined model incorporating the total CSVD burden score can effectively improve the predictive efficacy.

Key words: Cerebral small vessel disease; Cognitive impairment; Precursor of brain-derived neurotrophic factor; Tissue-type plasminogen activator

摘要： 目的探讨血浆脑源性神经营养因子前体（precursor of brain-derived neurotrophic factor，proBDNF）、成熟型脑源性神经营养因子（mature brain-derived neurotrophic factor，mBDNF）及组织型纤溶酶原激活物（tissue-type plasminogen activator，t-PA）水平对脑小血管病（cerebral small vessel disease，CSVD）认知障碍的预测价值及相关机制。
方法采用横断面病例对照设计，纳入2021年11月—2022年11月于昆明医科大学第二附属医院神经内科就诊的CSVD患者，并根据患者受教育程度和MoCA总分分为CSVD认知正常组、CSVD认知障碍组。同时选取同期健康体检者或CSVD患者家属、陪护人员中的合格志愿者作为对照组。采用酶联免疫吸附测定法检测血浆proBDNF、mBDNF、t-PA浓度；使用CSVD总负担评分（0～4分）评估CSVD总负担；采用MoCA进行认知功能评定。通过协方差分析校正混杂因素，比较三组间血浆生物标志物水平差异；基于偏相关分析，探讨血浆生物标志物水平与MoCA总分的相关性；采用ROC曲线评估血浆生物标志物水平及联合模型对CSVD认知障碍与CSVD认知正常的区分效能。
结果共纳入受试者131例，其中对照组32例，CSVD认知正常组38例，CSVD认知障碍组61例。校正混杂因素后，CSVD认知障碍组血浆proBDNF水平低于CSVD认知正常组和对照组，血浆mBDNF水平低于对照组，血浆t-PA水平高于对照组（均P<0.05）。偏相关分析显示，血浆proBDNF、mBDNF水平均与MoCA总分呈正相关（r=0.439，P<0.001；r=0.269，P=0.007），血浆t-PA水平与MoCA总分呈负相关（r=-0.270，P=0.007）。ROC曲线分析显示，血浆proBDNF、t-PA水平在区分CSVD认知障碍与CSVD认知正常时，具有中等预测价值（AUC 0.709，P<0.001；AUC 0.684，P<0.001）。基于血浆proBDNF、mBDNF、t-PA水平及CSVD总负担评分构建的联合模型预测效能最优（AUC 0.844，95%CI 0.779～0.908）。
结论 CSVD认知障碍患者的血浆proBDNF、mBDNF水平降低，t-PA水平升高，且其变化与认知功能损害程度相关。血浆proBDNF、t-PA水平对CSVD认知障碍具有中等预测价值，联合CSVD总负担评分构建的联合模型，可有效提升预测效能。

关键词: 脑小血管病; 认知障碍; 脑源性神经营养因子前体; 组织型纤溶酶原激活物

CLC Number:

XIONG Jing, LIU Feng, LI Xinrui, LIU Limin, LIU Hongming, LI Yunyuan. Predictive Value and Mechanism of Plasma proBDNF, mBDNF, and t-PA Levels for Cognitive Impairment in Cerebral Small Vessel Disease [J]. Chinese Journal of Stroke, 2026, 21(3): 293-302.

熊静, 刘凤, 李馨蕊, 刘利民, 刘宏明, 李云媛. 血浆proBDNF、mBDNF与t-PA水平对脑小血管病认知障碍的预测价值及机制探讨[J]. 中国卒中杂志, 2026, 21(3): 293-302.

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URL: https://www.chinastroke.org.cn/EN/10.3969/j.issn.1673-5765.2026.03.005

https://www.chinastroke.org.cn/EN/Y2026/V21/I3/293

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