Evaluation of a novel immunoassay to detect p-tau Thr217 in the CSF to distinguish Alzheimer disease from other dementias.
Evaluation of a novel immunoassay to detect p-tau Thr217 in the CSF to distinguish Alzheimer disease from other dementias.
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DOI：
10.1212/wnl.0000000000010814
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发表时间：
2020-12-01
期刊：
影响因子：
9.9
通讯作者：
Zilka N
中科院分区：
文献类型：
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作者：
Hanes J;Kovac A;Kvartsberg H;Kontsekova E;Fialova L;Katina S;Kovacech B;Stevens E;Hort J;Vyhnalek M;Boonkamp L;Novak M;Zetterberg H;Hansson O;Scheltens P;Blennow K;Teunissen CE;Zilka N
探讨脑脊液中Thr217蛋白磷酸化的tau蛋白（p-tau T217）测定是否可以区分阿尔茨海默病（AD）患者与其他痴呆患者和健康对照。我们开发并验证了一种新的Simoa免疫分析法来检测脑脊液中的p-tau T217。共有190名参与者来自3个队列，分别患有AD （n = 77）和其他神经退行性疾病（n = 69）以及健康参与者（n = 44）。与p-tau T181 ELISA （52 pg/mL）相比，p-tau T217检测（截止值242 pg/mL）识别AD患者的准确性为90%，阳性预测值（PPV）为78%，阴性预测值（NPV）为97%，敏感性为93%，特异性为88%，准确性为78%，PPV为58%，NPV为98%，特异性为71%，敏感性为97%。该检测将AD患者与年龄匹配的健康对照区分开来（临界值为163 pg/mL，灵敏度98%，特异性93%），类似于p-tau T181 ELISA（临界值为60 pg/mL，灵敏度96%，特异性86%）。在AD患者中，我们发现p-tau T217和p-tau T181、总tau和β-淀粉样蛋白40之间有很强的相关性，但β-淀粉样蛋白42没有相关性。本研究表明，p-tau T217比p-tau T181具有更好的诊断准确性。这些数据表明，新的p-tau T217检测方法在临床评价中具有作为AD诊断试验的潜力。这项研究提供了III类证据，证明脑脊液中p-tau T217的免疫测定可以将AD患者与其他痴呆症患者和健康对照患者区分开来。
To investigate whether tau phosphorylated at Thr217 (p-tau T217) assay in CSF can distinguish patients with Alzheimer disease (AD) from patients with other dementias and healthy controls. We developed and validated a novel Simoa immunoassay to detect p-tau T217 in CSF. There was a total of 190 participants from 3 cohorts with AD (n = 77) and other neurodegenerative diseases (n = 69) as well as healthy participants (n = 44). The p-tau T217 assay (cutoff 242 pg/mL) identified patients with AD with accuracy of 90%, with 78% positive predictive value (PPV), 97% negative predictive value (NPV), 93% sensitivity, and 88% specificity, compared favorably with p-tau T181 ELISA (52 pg/mL), showing 78% accuracy, 58% PPV, 98% NPV, 71% specificity, and 97% sensitivity. The assay distinguished patients with AD from age-matched healthy controls (cutoff 163 pg/mL, 98% sensitivity, 93% specificity), similarly to p-tau T181 ELISA (cutoff 60 pg/mL, 96% sensitivity, 86% specificity). In patients with AD, we found a strong correlation between p-tau T217 and p-tau T181, total tau and β-amyloid 40, but not β-amyloid 42. This study demonstrates that p-tau T217 displayed better diagnostic accuracy than p-tau T181. The data suggest that the new p-tau T217 assay has potential as an AD diagnostic test in clinical evaluation. This study provides Class III evidence that a CSF immunoassay for p-tau T217 distinguishes patients with AD from patients with other dementias and healthy controls.