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_Lilly, p-tau217_Lilly) 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_Lilly 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_Lilly showed stronger correlations with Aβ- and tau-PET (p < 0.0001). P-Tau217_Lilly 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 [p < 0.0001] - 0.96 [p < 0.05]) and for identifying Aβ-PET (AUC, 0.86 vs 0.74 [p < 0.0001] and 0.83 [p < 0.001]) and tau-PET positivity (AUC, 0.94 vs 0.80—0.92, p < 0.0001). Finally, p-Tau181_Lilly generally performed better than the other p-tau181 assays (e.g., AD dementia vs non-AD, AUC, 0.96 vs 0.88 [p-tau181_Innotest] and 0.89 [p-tau181_Elecsys]; p < 0.0001).

CSF p-tau217_Lilly 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.

CSF 中的磷酸化 tau (p-tau) 被认为是阿尔茨海默病 (AD) 的重要生物标志物，并已纳入最近的诊断标准。存在几种变体，包括苏氨酸 181 (p-tau181)、217 (p-tau217) 和 231 (p-tau231) 处的 p-tau。然而，没有研究将它们的诊断性能或关联与 β-淀粉样蛋白 (Aβ) 和 tau-PET 进行比较。了解使用哪种 p-tau 变体仍然是一个重要但已回答的问题。我们旨在比较脑脊液中 p-tau181、p-tau217 和 p-tau231 对 AD 的诊断准确性及其与 Aβ 和 tau-PET 的关联。

瑞典 BioFINDER-2 研究共有 629 名参与者（认知未受损，n = 334；Aβ 阳性轻度认知障碍，n = 84；AD 痴呆，n = 119；非 AD 障碍，n = 92） . 除了使用礼来 (p-tau181 _Lilly , p-tau217 _Lilly ) 和 p-tau231的相同检测抗体的测定法测量p-tau181和 p-tau217 外，我们还包括了来自 2 个常用测定法的 p-tau181 测量值（ Innotetest 和 Elecsys）。

尽管所有 p-tau 变体在整个 AD 连续体中都增加了，但 p-tau217 _Lilly显示出最大的动态范围（AD 痴呆与非 AD 的其他 p-tau 变体增加 13 倍相比增加 1.9-5.4 倍）。P-Tau217 _Lilly显示出与 Aβ- 和 tau-PET 更强的相关性 ( p < 0.0001)。P-Tau217 _Lilly在区分 AD 痴呆与非 AD 方面表现出比其他 p-tau 变体更高的准确度（曲线下面积 [AUC]，0.98 对 0.88 [ p < 0.0001] - 0.96 [ p < 0.05]）和识别 Aβ -PET（AUC，0.86 对 0.74 [ p < 0.0001] 和 0.83 [ p < 0.001]）和 tau-PET 阳性（AUC，0.94 对 0.80-0.92，p< 0.0001)。最后，对- Tau181 _Lilly公司通常比其它的p tau181测定表现较好（例如，AD痴呆与非AD，AUC，0.96 VS 0.88 [P-tau181 _INNOTEST ]和0.89 [P-tau181 _{Elecsys测定}]; p <0.0001） .

在 AD 的检查中，CSF p-tau217 _Lilly似乎比其他包含的 p-tau 检测更有用。p-tau181 检测的不同结果凸显了抗 tau 抗体对生物标志物性能的重要性。

该研究提供了 II 类证据，即 p-tau217 对 AD 痴呆的诊断提供比 p-tau181 或 p-tau231 更高的诊断准确性。