Evaluation of CSF-tau and CSF-Aβ42 as diagnostic markers for Alzheimer disease in clinical practice
Evaluation of CSF-tau and CSF-Aβ42 as diagnostic markers for Alzheimer disease in clinical practice
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DOI：
10.1001/archneur.58.3.373
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发表时间：
2001-03-01
影响因子：
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通讯作者：
Blennow, K
中科院分区：
文献类型：
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作者：
Andreasen, N;Minthon, L;Blennow, K
目的：探讨脑脊液(CSF)中42位氨基酸终止蛋白(Aβ42)和tau蛋白水平作为阿尔茨海默病(AD)生物标志物的诊断价值。设计：一项为期一年的前瞻性研究。地点：瑞典皮特亚河谷医院收治的所有认知症状患者，均为社区人群样本。患者：共241例，其中疑似AD 105例，疑似AD 58例，血管性痴呆23例，轻度认知损害20例；路易体痴呆(n=9)、其他神经系统疾病(n=3)、精神障碍(n=5)和非痴呆者(n=18)。主要观察指标：脑脊液tau和脑脊液Aβ42作为常规临床神经化学分析。敏感度和特异度使用来自多中心研究的100名对照受试者的回归线来定义。计算不同AD患病率的阳性预测值和阴性预测值。结果：我们发现在可能和可能的AD患者中，CSF-tau升高，而CSF-Aβ42水平降低。对可能的AD的敏感性为94%，对可能的AD的敏感性为88%，对轻度认知障碍的敏感性为75%，而对精神障碍的特异性为100%，对非痴呆的特异性为89%。在路易体痴呆患者中，特异性较低(67%)，主要是因为脑脊液-Aβ42水平较低；在血管性痴呆患者中，特异性较低(48%)，主要是因为脑脊液-tau水平较高。携带载脂蛋白E epsilon4等位基因的AD患者对CSF-tau和CSF-Aβ42的敏感性增加，接近100%。在AD患病率为45%时，阳性预测值为90%，阴性预测值为95%。结论：到目前为止，脑脊液tau和CSF-Aβ42已经在研究环境中进行了研究，条件是在主导数据的情况下表现最佳。我们检查了一个潜在的患者样本，按照临床常规进行分析，得出的数据更接近于脑脊液-tau和脑脊液Aβ42的真实表现。AD的预测值大于90%。因此，这些生物标志物可能在认知障碍患者的临床工作中发挥作用，特别是在区分早期AD与正常衰老和精神障碍方面。
Objective: To evaluate the diagnostic potential of cerebrospinal fluid (CSF) levels of tau and beta -amyloid protein ending at amino acid 42 (A beta 42) as biomarkers for Alzheimer disease (AD) in clinical practice.Design: A 1-year prospective study.Setting: Community population-based sample of all consecutive patients admitted for investigation of cognitive symptoms to the Pitea River Valley Hospital, Pitea, Sweden.Patients: A total of 241 patients with probable AD (n = 105), possible AD (n= 58), vascular dementia (n= 23), mild cognitive impairment (n=20); Lewy body dementia (n=9), other neurological disorders (n=3), and psychiatric disorders (n=5) and nondemented individuals (n= 18).Main Outcome Measures: Cerebrospinal fluid tau and CSF-A beta 42 were assayed each week as routine clinical neu rochemical analyses. Sensitivity and specificity were defined using the regression line from 100 control subjects from a multicenter study. Positive and negative predictive values were calculated for different prevalence rates of AD.Results: We found increased CSF-tau and decreased CSF-A beta 42 levels in probable and possible AD. Sensitivity was 94% for probable AD, 88% for possible AD, and 75% for mild cognitive impairment, whereas specificity was 100% for psychiatric disorders and 89% for nondemented. Specificity was lower in Lewy body dementia (67%) mainly because of low CSF-A beta 42 levels and in vascular dementia (48%) mainly because of high CSF-tau levels. Sensitivity for CSF-tau and CSF-A beta 42 increased in patients with AD possessing the ApoE epsilon4 allele, approaching 100%. At a prevalence of AD of 45%, the positive predictive value was 90% and the negative predictive value was 95%.Conclusions: Cerebrospinal fluid tau and CSF-A beta 42 have so far been studied in research settings, under conditions presiding data on the optimal performance. We examined a prospective patient sample, with assays run in clinical routine, giving figures closer to the true performance of CSF-tau and CSF-A beta 42. The predictive value for AD was greater than 90%. Therefore, these biomarkers may have a role in the clinical workup of patients with cognitive impairment, especially to differentiate early AD from normal aging and psychiatric disorders.