Antibody-based immunoassays have enabled quantification of very low concentrations of phosphorylated tau (p-tau) protein forms in cerebrospinal fluid (CSF), aiding in the diagnosis of AD. Mass spectrometry enables absolute quantification of multiple p-tau variants within a single run. The goal of this study was to compare the performance of mass spectrometry assessments of p-tau181, p-tau217 and p-tau231 with established immunoassay techniques. We measured p-tau181, p-tau217 and p-tau231 concentrations in CSF from 173 participants from the TRIAD cohort and 394 participants from the BioFINDER-2 cohort using both mass spectrometry and immunoassay methods. All subjects were clinically evaluated by dementia specialists and had amyloid-PET and tau-PET assessments. Bland–Altman analyses evaluated the agreement between immunoassay and mass spectrometry p-tau181, p-tau217 and p-tau231. P-tau associations with amyloid-PET and tau-PET uptake were also compared. Receiver Operating Characteristic (ROC) analyses compared the performance of mass spectrometry and immunoassays p-tau concentrations to identify amyloid-PET positivity. Mass spectrometry and immunoassays of p-tau217 were highly comparable in terms of diagnostic performance, between-group effect sizes and associations with PET biomarkers. In contrast, p-tau181 and p-tau231 concentrations measured using antibody-free mass spectrometry had lower performance compared with immunoassays. Our results suggest that while similar overall, immunoassay-based p-tau biomarkers are slightly superior to antibody-free mass spectrometry-based p-tau biomarkers. Future work is needed to determine whether the potential to evaluate multiple biomarkers within a single run offsets the slightly lower performance of antibody-free mass spectrometry-based p-tau quantification.

中文翻译：

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免疫测定法与质谱法衍生的 p-tau 定量检测阿尔茨海默病病理学的比较

基于抗体的免疫测定能够对脑脊液 (CSF) 中极低浓度的磷酸化 tau (p-tau) 蛋白形式进行定量，从而有助于 AD 的诊断。质谱法可以在单次运行中对多个 p-tau 变体进行绝对定量。本研究的目的是将 p-tau181、p-tau217 和 p-tau231 的质谱评估性能与已建立的免疫测定技术进行比较。我们使用质谱和免疫分析方法测量了来自 TRIAD 队列的 173 名参与者和来自 BioFINDER-2 队列的 394 名参与者的 CSF 中 p-tau181、p-tau217 和 p-tau231 浓度。所有受试者均由痴呆症专家进行临床评估，并进行淀粉样蛋白 PET 和 tau-PET 评估。Bland-Altman 分析评估了免疫分析和质谱分析 p-tau181、p-tau217 和 p-tau231 之间的一致性。还比较了 P-tau 与淀粉样蛋白-PET 和 tau-PET 摄取的关联。受试者操作特征 (ROC) 分析比较了质谱法和免疫测定 p-tau 浓度的性能，以确定淀粉样蛋白 PET 阳性。p-tau217 的质谱分析和免疫分析在诊断性能、组间效应大小以及与 PET 生物标志物的关联方面具有高度可比性。相反，与免疫测定相比，使用无抗体质谱法测量的 p-tau181 和 p-tau231 浓度的性能较低。我们的结果表明，虽然总体相似，但基于免疫测定的 p-tau 生物标志物略优于基于无抗体质谱的 p-tau 生物标志物。未来的工作需要确定单次运行中评估多个生物标志物的潜力是否可以抵消基于无抗体质谱法的 p-tau 定量的稍低性能。