脑脊液tau蛋白含量测定对阿尔茨海默病的诊断价值

目的 探讨可信的阿尔茨海默病（AD）临床诊断的生化指标。方法 用ELISA－双酶底物循环扩增技术检测AD（52例）、血管性痴呆（VD,46例）、非痴呆性神经系统疾病（non-AD,37例）和正常对照组（56例）的脑脊液（CSF）中tau蛋白和磷酸化tau(p-tau)含量。结果 测定经国外尸检组织病理学确诊的AD CSF样品组的总tau和p-tau含量,显著高于VD组、non-AD组及正常对照组;二者的灵敏度、特异性、可靠性及与VD的鉴别率分别为90．0％、79．0％、82．8％、66．7％和93．3％、89．5％、90．8％、83．3％。测定国内从多家医院收集的CSF样品组的总tau和p-tau的含量,亦呈类似结果。其p-tau的灵敏度、特异性、可靠性及与VD鉴别率分别为77．3％、85．4％、83．7％和71．4％。结论 CSFp-tau测定是可信的AD临床诊断生化指标。

Diagnostic value of tau in cerebrospinal fluid in alzheimer disease

OBJECTIVE: To search for reliable and quantitative biochemical marker for diagnosis of Alzheimer disease. METHODS: ELISA-double enzyme amplification assay was used to detect the total tau and abnormally hyperphosphorylated (p-tau) in cerebrospinal fluid specimens of patients with Alzheimer disease (AD, N = 52, 30 from the Netherlands and 22 from Wuhan and Haikou, China), vascular dementia (VD, N = 46, 18 from the Netherlands and 28 from Haikou), and non-neurological disease (N = 37, 13 from the Netherlands and 24 from Haikou) and of normal elderly controls (N = 56, 26 from the Netherlands, and 30 from Wuan and Haikou). RESULTS: The measurement of CSF specimens from Netherlands Brain Bank showed that the levels of total tau and p-tau in CSF specimens of AD patients were significantly higher than those in CSF of patients with VD and non-dementia neurological disorders, and of age-matched non-neurological normal controls. With CSF tau > or = 370 pg/ml as the marker for diagnosis of AD, the sensitivity, specificity, reliability as well as differentiation rate of AD from VD were 90.0%, 79.0%, 82.8% and 66.7%, respectively. With CSF p-tau > or = 120 pg/ml as the marker for diagnosis of AD, the sensitivity, specificity, reliability as well as differentiation rate of AD from VD were 93.3%, 89.5%, 90.8%, and 83.3% respectively. The measurement of total and phosphorylated taus in CSF specimens of AD and non-AD patients and normal controls collected in China showed the similar results; and the sensitivity, specificity, reliability as well as differentiation rate of AD from VD were 77.3%, 85.4%, 83.7% and 71.4% with CSF tau > or = 120 pg/ml as the marker for diagnosis of AD. There was no correlation between CSF tau and p-tau and age, sex, and seriousness of disease. CONCLUSION: Increased phosphorylated tau in human cerebrospinal fluid is a reliable biomarker for diagnosis of Alzheimer disease.