Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre Intégré Universitaire de Santé Et de Services Sociaux (CIUSSS) de l'Ouest-de-L'Île-de-Montréal, 6875 La Salle Blvd - FBC Room 3149, Montréal, Québec, H4H 1R3, Canada.
Department of Neurology and Neurosurgery, McGill University, Montreal, QC, H3A 2B4, Canada.
Mol Neurodegener. 2024 Jan 7;19(1):2. doi: 10.1186/s13024-023-00689-2.
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-tau, p-tau and p-tau with established immunoassay techniques.
We measured p-tau, p-tau and p-tau 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-tau, p-tau and p-tau. 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-tau were highly comparable in terms of diagnostic performance, between-group effect sizes and associations with PET biomarkers. In contrast, p-tau and p-tau 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.
基于抗体的免疫分析使人们能够定量检测脑脊液（CSF）中极低浓度的磷酸化 tau（p-tau）蛋白形式，有助于 AD 的诊断。质谱分析能够在单次运行中对多种 p-tau 变体进行绝对定量。本研究的目的是比较质谱分析 p-tau、p-tau 和 p-tau 与已建立的免疫分析技术的性能。
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 BioFINDER-2 队列的 394 名参与者的 CSF 中的 p-tau、p-tau 和 p-tau 浓度。所有受试者均由痴呆症专家进行临床评估，并进行了淀粉样蛋白-PET 和 tau-PET 评估。Bland-Altman 分析评估了免疫分析和质谱 p-tau、p-tau 和 p-tau 之间的一致性。还比较了 p-tau 与淀粉样蛋白-PET 和 tau-PET 摄取的相关性。接收者操作特征（ROC）分析比较了质谱和免疫分析 p-tau 浓度的性能，以识别淀粉样蛋白-PET 阳性。
质谱和免疫分析 p-tau 在诊断性能、组间效应大小和与 PET 生物标志物的相关性方面高度可比。相比之下，使用无抗体质谱法测量的 p-tau 和 p-tau 浓度的性能与免疫分析相比略低。
我们的结果表明，虽然总体上相似，但基于免疫分析的 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。需要进一步的工作来确定是否在单次运行中评估多种生物标志物的潜力可以弥补基于无抗体质谱的 p-tau 定量的性能略低的问题。
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