From the AXON Neuroscience R&D Services SE (J. Hanes, A.K., E.K., L.F., B.K., E.S., N.Z.), Bratislava, Slovakia; Department of Psychiatry and Neurochemistry (H.K., H.Z., K.B.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal; Clinical Neurochemistry Laboratory (H.K., H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; AXON Neuroscience CRM Services SE (S.K.), Bratislava, Slovakia; International Clinical Research Centre (J. Hort, M.V.), St. Anne's University Hospital Brno; Memory Clinic, Department of Neurology (J. Hort, M.V.), Charles University, 2nd Faculty of Medicine and Motol University Hospital, Czech Republic; Department of Clinical Chemistry, Neurochemistry Laboratory (L.B., C.E.T.), Amsterdam Neuroscience, VU University Medical Center Amsterdam, the Netherlands; Axon Neuroscience SE (M.N.), Larnaca, Cyprus; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square, London; UK Dementia Research Institute at UCL (H.Z.), London; Clinical Memory Research Unit (O.H.), Department of Clinical Sciences Malmö, Lund University; Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden; and Department of Neurology, Alzheimer Center (P.S.), Amsterdam Neuroscience, the Netherlands.
Neurology. 2020 Dec 1;95(22):e3026-e3035. doi: 10.1212/WNL.0000000000010814. Epub 2020 Sep 24.
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.
研究脑脊液中 tau 磷酸化在 Thr217 位（p-tau T217）的测定能否区分阿尔茨海默病（AD）患者与其他痴呆患者和健康对照者。
我们开发并验证了一种新的 Simoa 免疫分析法来检测 CSF 中的 p-tau T217。共有来自 3 个队列的 190 名参与者，包括 AD 患者（n=77）、其他神经退行性疾病患者（n=69）和健康对照者（n=44）。
p-tau T217 检测（cutoff 242 pg/mL）对 AD 患者的识别准确率为 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%，与 p-tau T181 ELISA（cutoff 52 pg/mL）相比具有更好的性能，其准确率为 78%，PPV 为 58%，NPV 为 98%，特异性为 71%，敏感性为 97%。该检测方法能够将 AD 患者与年龄匹配的健康对照者区分开（cutoff 163 pg/mL，敏感性为 98%，特异性为 93%），与 p-tau T181 ELISA（cutoff 60 pg/mL，敏感性为 96%，特异性为 86%）相似。在 AD 患者中，我们发现 p-tau T217 与 p-tau T181、总 tau 和 β-淀粉样蛋白 40 之间存在很强的相关性，但与 β-淀粉样蛋白 42 无相关性。
本研究表明，p-tau T217 的诊断准确性优于 p-tau T181。数据表明，新的 p-tau T217 检测具有作为 AD 临床评估中诊断测试的潜力。
本研究提供了 III 级证据，表明 CSF 中 p-tau T217 的免疫测定能够区分 AD 患者与其他痴呆患者和健康对照者。
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