From the Clinical Memory Research Unit (A.L., S.J., N.M.-C., S.P., C.C., E.S., O.H.), Department of Clinical Sciences, Lund University, Malmö; Department of Neurology (N.M.-C.) and Memory Clinic (S.P., E.S., O.H.), Skåne University Hospital, Lund; Wallenberg Centre for Molecular Medicine (N.M.-C.), Lund University, Sweden; ADx NeuroSciences NV (D.J., E.V.), Ghent, Belgium; and Eli Lilly and Company (J.L.D.), Indianapolis, IN.
Neurology. 2021 Oct 26;97(17):e1681-e1694. doi: 10.1212/WNL.0000000000012727. Epub 2021 Sep 7.
Phosphorylated tau (p-tau) in CSF is considered an important biomarker in Alzheimer disease (AD) and has been incorporated in recent diagnostic criteria. Several variants exist, including p-tau at threonines 181 (p-tau181), 217 (p-tau217), and 231 (p-tau231). However, no studies have compared their diagnostic performance or association to β-amyloid (Aβ) and tau-PET. Understanding which p-tau variant to use remains an important yet answered question. We aimed to compare the diagnostic accuracy of p-tau181, p-tau217, and p-tau231 in CSF for AD and their association with Aβ and tau-PET.
A total of 629 participants in the Swedish BioFINDER-2 study were included (cognitively unimpaired, n = 334; Aβ-positive mild cognitive impairment, n = 84; AD dementia, n = 119; and non-AD disorders, n = 92). In addition to p-tau181 and p-tau217 measured using assays with the same detector antibodies from Eli Lilly (p-tau181, p-tau217) and p-tau231, we also included p-tau181 measurements from 2 commonly used assays (Innotest and Elecsys).
Although all p-tau variants increased across the AD continuum, p-tau217 showed the greatest dynamic range (13-fold increase vs 1.9-5.4-fold increase for other p-tau variants for AD dementia vs non-AD). P-Tau217 showed stronger correlations with Aβ- and tau-PET ( < 0.0001). P-Tau217 exhibited higher accuracy than other p-tau variants for separating AD dementia from non-AD (area under the curve [AUC], 0.98 vs 0.88 [ < 0.0001] - 0.96 [ < 0.05]) and for identifying Aβ-PET (AUC, 0.86 vs 0.74 [ < 0.0001] and 0.83 [ < 0.001]) and tau-PET positivity (AUC, 0.94 vs 0.80-0.92, < 0.0001). Finally, p-Tau181 generally performed better than the other p-tau181 assays (e.g., AD dementia vs non-AD, AUC, 0.96 vs 0.88 [p-tau181] and 0.89 [p-tau181]; < 0.0001).
CSF p-tau217 seems to be more useful than other included p-tau assays in the workup of AD. Varied results across p-tau181 assays highlights the importance of anti-tau antibodies for biomarker performance.
This study provides Class II evidence that p-tau217 provides higher diagnostic accuracy for diagnosis of AD dementia than p-tau181 or p-tau231.
脑脊液中的磷酸化 tau（p-tau）被认为是阿尔茨海默病（AD）的一个重要生物标志物，并已被纳入最近的诊断标准。存在多种变体，包括 threonine 181（p-tau181）、217（p-tau217）和 231（p-tau231）处的磷酸化 tau。然而，尚无研究比较它们的诊断性能或与β-淀粉样蛋白（Aβ）和 tau-PET 的关联。了解使用哪种 p-tau 变体仍然是一个重要但尚未解决的问题。我们旨在比较 CSF 中 p-tau181、p-tau217 和 p-tau231 对 AD 的诊断准确性及其与 Aβ 和 tau-PET 的相关性。
共有 629 名参加瑞典 BioFINDER-2 研究的参与者被纳入研究（认知正常，n=334；Aβ 阳性轻度认知障碍，n=84；AD 痴呆，n=119；非 AD 疾病，n=92）。除了使用来自 Eli Lilly 的具有相同检测抗体的测定法测量 p-tau181 和 p-tau217（p-tau181、p-tau217）和 p-tau231 外，我们还包括了两种常用测定法（Innotest 和 Elecsys）的 p-tau181 测量结果。
尽管所有 p-tau 变体在 AD 连续体中均增加，但 p-tau217 显示出最大的动态范围（AD 痴呆症与非 AD 相比，p-tau217 的增加倍数为 13 倍，而其他 p-tau 变体的增加倍数为 1.9-5.4 倍）。p-tau217 与 Aβ-和 tau-PET 的相关性更强（<0.0001）。p-tau217 在区分 AD 痴呆症与非 AD（曲线下面积[AUC]，0.98 与 0.88[<0.0001]-0.96[<0.05]）和识别 Aβ-PET（AUC，0.86 与 0.74[<0.0001]和 0.83[<0.001]）和 tau-PET 阳性率（AUC，0.94 与 0.80-0.92，<0.0001）方面的准确性均高于其他 p-tau 变体。最后，p-tau181 通常比其他 p-tau181 测定法表现更好（例如，AD 痴呆症与非 AD，AUC，0.96 与 0.88[p-tau181]和 0.89[p-tau181]；<0.0001）。
CSF p-tau217 似乎比其他纳入的 p-tau 测定法在 AD 的评估中更有用。p-tau181 测定法的结果差异突出了抗 tau 抗体对生物标志物性能的重要性。
本研究提供了 II 级证据，表明 p-tau217 对 AD 痴呆症的诊断准确性高于 p-tau181 或 p-tau231。
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