慢性创伤性脑病诊断相关标志物的研究进展

doi:10.3877/cma.j.issn.2095-9141.2022.05.009

慢性创伤性脑病（CTE）是一种与头部反复创伤相关的神经退行性疾病，以脑内大量磷酸化Tau蛋白异常积聚为特征。CTE晚期可引起认知和行为功能障碍，甚至引起痴呆和自杀，严重影响患者的生活质量。目前，CTE缺乏客观的诊断标志物，导致临床诊断非常困难，通常只能依靠尸检进行确诊，给家庭和社会带来严重负担。CTE诊断相关生物标志物在评估损伤程度、早期诊断、制定治疗方案等方面具有重要临床价值。本文围绕与CTE诊断相关的脑脊液、血液及其他生物标志物进行综述，以期为早期诊断及临床治疗提供参考和借鉴。

关键词: 慢性创伤性脑病, 诊断标志物, 磷酸化Tau蛋白, 脑脊液

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive head trauma, which characterized by abnormal accumulation of a large number of phosphorylated Tau protein in the brain. Severe cognitive and behavior disfunction, and even dementia or suicide may occur in later stages of CTE, which seriously impacts the life quality of patients. At present, clinical diagnosis of CTE is very difficult due to a lack of objective diagnostic biomarkers, and diagnosis can only be made by autopsy, putting a heavy burden on family and society. The biomarkers related to CTE diagnosis have important clinical value in assessing the degree of injury, early diagnosis, and treatment protocol decision-making, etc.. Therefore, this review was conducted by analyzing and summaring the cerebrospinal fluid blood and other related biomarkers associated with CTE diagnosis, in order to provide reference for early diagnosis and clinical treatment.

Key words: Chronic traumatic encephalopathy, Diagnostic biomarkers, Phosphorylated Tau protein, Cerebrospinal fluid

表1 慢性创伤性脑病诊断标志物

标志物		生物功能	意义	参考文献
脑脊液标志物
	p-Tau	与轴突损伤相关	p-Tau蛋白水平与反复创伤严重程度相关，颅脑创伤后在脑脊液中升高	[12,13,14]
	NFL	存在于神经元细胞质中，是神经元细胞骨架成分	轴突损伤最具有代表性的标志物	[17,18]
	Aβ	易引起神经元损伤或死亡，导致神经退行性病变	特异性不高，与年龄相关	[19,20,21]
	GFAP	仅由星形胶质细胞表达，在细胞骨架受损后释放	脑损伤后升高，标志着神经胶质细胞增生和神经炎症，已被用作短期内神经退行性疾病进展的衡量标准	[22,23,24]
	S100β	钙结合蛋白，参与很多病理生理反应，并能预测神经系统的损伤	特异性差，其他细胞也可以分泌	[27,28,29]
血液标志物
	UCH-L1	清除神经元中错误折叠、氧化或过量的蛋白质	在慢性神经退行性疾病中广泛应用，但灵敏度低	[32,33]
	NSE	神经细胞损伤或坏死后升高	灵敏度低	[34,35]
	miRNA	调控中枢神经系统正常运行	特异性高，灵敏度高	[37,38,39,40]
其他标志物
	炎性因子	神经炎症贯穿颅脑损伤的全过程	特异性差，灵敏度低	[41,42,43]
	影像标志	正电子发射断层扫描成像	成像耗时且昂贵	[44,48]

表1 慢性创伤性脑病诊断标志物

标志物		生物功能	意义	参考文献
脑脊液标志物
	p-Tau	与轴突损伤相关	p-Tau蛋白水平与反复创伤严重程度相关，颅脑创伤后在脑脊液中升高	[12,13,14]
	NFL	存在于神经元细胞质中，是神经元细胞骨架成分	轴突损伤最具有代表性的标志物	[17,18]
	Aβ	易引起神经元损伤或死亡，导致神经退行性病变	特异性不高，与年龄相关	[19,20,21]
	GFAP	仅由星形胶质细胞表达，在细胞骨架受损后释放	脑损伤后升高，标志着神经胶质细胞增生和神经炎症，已被用作短期内神经退行性疾病进展的衡量标准	[22,23,24]
	S100β	钙结合蛋白，参与很多病理生理反应，并能预测神经系统的损伤	特异性差，其他细胞也可以分泌	[27,28,29]
血液标志物
	UCH-L1	清除神经元中错误折叠、氧化或过量的蛋白质	在慢性神经退行性疾病中广泛应用，但灵敏度低	[32,33]
	NSE	神经细胞损伤或坏死后升高	灵敏度低	[34,35]
	miRNA	调控中枢神经系统正常运行	特异性高，灵敏度高	[37,38,39,40]
其他标志物
	炎性因子	神经炎症贯穿颅脑损伤的全过程	特异性差，灵敏度低	[41,42,43]
	影像标志	正电子发射断层扫描成像	成像耗时且昂贵	[44,48]

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Advances in diagnostic markers of chronic traumatic encephalopathy

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Advances in diagnostic markers of chronic traumatic encephalopathy