Bali Divya, Salvadó Gemma, Beach Thomas G, Serrano Geidy E, Atri Alireza, Reiman Eric M, Jeromin Andreas, Hansson Oskar, Janelidze Shorena
Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Sölvegatan 19, BMC B11, Lund, 22184, Sweden.
Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, 10515 W Santa Fe Drive, Sun City, Arizona, 85351, USA.
Acta Neuropathol Commun. 2025 Jun 30;13(1):144. doi: 10.1186/s40478-025-02064-2.
There is an urgent need for accurate and validated methods to measure plasma phosphorylated tau (p-Tau) biomarkers in Alzheimer's disease (AD). In this study, we compared the performance of new commercially available plasma p-Tau217 assay developed by ALZpath to other established p-Tau assays in an autopsy-confirmed sample. We included 72 participants from the Arizona Study of Aging and Neurodegenerative Disorders cohort, with antemortem plasma assessments and postmortem neuropathological examination. Plasma p-Tau217 was measured using the single molecule arrays (SIMOA)-based ALZpath immunoassay and plasma p-Tau217 and p-Tau181 were analyzed with mesoscale discovery (MSD)-based immunoassays developed by Lilly Research Laboratories. Plasma biomarkers were compared with densities of post-mortem-assessed amyloid plaques and neurofibrillary changes. Levels of p-Tau217, p-Tau217 and p-Tau181 were significantly associated with plaque (partial Spearman ρ = 0.58, ρ = 0.78, ρ = 0.65; p < 0.001) and neurofibrillary (ρ = 0.26, ρ = 0.51, ρ = 0.37; p < 0.05) density scores, adjusting for age, sex, and time of interval between blood sampling and death. All three biomarkers were also significantly associated with plaque density scores (p-Tau217, ρ = 0.53; p-Tau217, ρ = 0.73; p-Tau181, ρ = 0.59; p < 0.001), when additionally adjusting for neurofibrillary density scores. However, only p-Tau217 was significantly associated with neurofibrillary density scores (ρ = 0.32, p = 0.022), when adjusting for plaque density scores. The correlations of p-Tau217 and p-Tau181 with plaque density scores were comparable, whereas p-Tau217 exhibited significantly higher correlations with plaques (p≤0.015) and neurofibrillary changes (p≤0.004) than p-Tau217. While p-Tau217 and p-Tau181 predicted the presence of Alzheimer's disease neuropathological change (ADNC), Braak staging (Braak 0-IV vs. Braak V-VI) and CERAD neuritic plaque classification (low/sparse vs. moderate/frequent) with similar accuracies (area under the curve [AUC], 0.74-0.79), p-Tau217 AUCs were significantly higher (AUC,0.82-0.89, p≤0.024) than the AUCs of p-Tau217. In conclusion, p-Tau217 exhibited similar performance as p-Tau181 but its correlations with core measures of AD pathology were significantly lower in comparison with p-Tau217. Future studies are warranted to replicate these findings in larger independent cohorts.
迫切需要准确且经过验证的方法来测量阿尔茨海默病（AD）患者血浆中的磷酸化tau（p-Tau）生物标志物。在本研究中，我们在经尸检确诊的样本中，将ALZpath公司新推出的商业化血浆p-Tau217检测方法与其他已确立的p-Tau检测方法的性能进行了比较。我们纳入了来自亚利桑那衰老与神经退行性疾病研究队列的72名参与者，他们均进行了生前血浆评估和死后神经病理学检查。使用基于单分子阵列（SIMOA）的ALZpath免疫测定法测量血浆p-Tau217，并使用礼来研究实验室开发的基于中尺度发现（MSD）的免疫测定法分析血浆p-Tau217和p-Tau181。将血浆生物标志物与死后评估的淀粉样斑块密度和神经原纤维变化进行比较。在调整年龄、性别以及采血与死亡之间的时间间隔后，p-Tau217、p-Tau217和p-Tau181的水平与斑块（偏斯皮尔曼相关系数ρ = 0.58、ρ = 0.78、ρ = 0.65；p < 0.001）和神经原纤维（ρ = 0.26、ρ = 0.51、ρ = 0.37；p < 0.05）密度评分显著相关。在进一步调整神经原纤维密度评分后，所有三种生物标志物也与斑块密度评分显著相关（p-Tau217，ρ = 0.53；p-Tau217，ρ = 0.73；p-Tau181，ρ = 0.59；p < 0.001）。然而，在调整斑块密度评分后，只有p-Tau217与神经原纤维密度评分显著相关（ρ = 0.32，p = 0.022）。p-Tau217和p-Tau181与斑块密度评分的相关性相当，而与p-Tau217相比，p-Tau217与斑块（p≤0.015）和神经原纤维变化（p≤0.004）的相关性显著更高。虽然p-Tau217和p-Tau181预测阿尔茨海默病神经病理学改变（ADNC）、Braak分期（Braak 0-IV与Braak V-VI）和CERAD神经炎性斑块分类（低/稀疏与中度/频繁）的准确率相似（曲线下面积[AUC]，0.74 - 0.79），但p-Tau217的AUC显著高于p-Tau217的AUC（AUC，0.82 - 0.89，p≤0.024）。总之，p-Tau217表现出与p-Tau181相似的性能，但与p-Tau217相比，其与AD病理学核心指标的相关性显著更低。未来的研究有必要在更大的独立队列中重复这些发现。
