LUMIPULSE G-automated immunoassays represent a widely used method for the quantification of Alzheimer’s disease (AD) biomarkers in the cerebrospinal fluid (CSF). Less invasive blood-based markers confer a promising tool for AD diagnosis at prodromal stages (mild cognitive impairment (MCI)). Highly sensitive assays for the quantification of amyloid-beta (Aβ) and phosphorylated Tau-181 (p-Tau181) in the blood are showing promising results. In this study, we evaluated the clinical performance of the recently available fully automated LUMIPULSE plasma marker assays for detecting brain AD pathology and for predicting progression from MCI to AD dementia stage. A retrospective exploratory cohort of 138 individuals (22 neurological controls [NC], 72 MCI, and 44 AD dementia patients) was included. Data regarding baseline CSF concentrations of Aβ42, Aβ40, t-Tau, and p-Tau181 was available and used to establish the presence of AD brain pathology. Baseline Aβ42, Aβ40, and p-Tau181 concentrations were determined in stored plasma samples using high-throughput fully automated LUMIPULSE assays. Progression from MCI to AD dementia was evaluated during follow-up (mean 6.4 ± 2.5 years). Moreover, a prospective validation cohort of 72 individuals with memory complaints underwent AD biomarker quantification, closely mirroring typical clinical practice. This cohort aimed to confirm the study’s main findings. In the exploratory cohort, correlations between CSF and plasma were moderate for p-Tau181 (ρ = 0.61, p < 0.001) and weak for Aβ42/Aβ40 ratio (ρ = 0.39, p < 0.001). Plasma p-Tau181 and p-Tau181/Aβ42 concentrations were significantly increased while Aβ42/Aβ40 was significantly decreased (p < 0.001) in patients with AD dementia and prodromal AD, as well as in individuals with CSF abnormal amyloid concentrations (A +). Plasma p-Tau181 showed a robust performance in differentiating patients clinically diagnosed as AD (AUC = 0.89; 95% CI 0.83–0.94); A + vs. A − (AUC = 0.84, 95% CI 0.77–0.91) and also in predicting conversion to AD dementia in MCI patients (AUC = 0.89, 95% CI 0.81–0.96). When tested in the validation cohort, plasma p-Tau181 displayed 83.3% of the overall percentage of agreement according to amyloid status. Our results show that the measurement of p-Tau181 in plasma has great potential as a non-invasive prognostic screening tool for implementation in a clinical setting.

中文翻译：

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探索全自动 LUMIPULSE G 血浆检测在检测阿尔茨海默病病理学方面的潜力

LUMIPULSE G 自动免疫测定是一种广泛使用的定量脑脊液 (CSF) 中阿尔茨海默病 (AD) 生物标志物的方法。侵入性较小的血液标记物为前驱阶段（轻度认知障碍（MCI））的 AD 诊断提供了一种有前途的工具。血液中β-淀粉样蛋白 (Aβ) 和磷酸化 Tau-181 (p-Tau181) 定量的高灵敏度检测显示出有希望的结果。在这项研究中，我们评估了最近推出的全自动 LUMIPULSE 血浆标记物检测的临床性能，该检测用于检测大脑 AD 病理并预测从 MCI 到 AD 痴呆阶段的进展。纳入了 138 名个体（22 名神经对照 [NC]、72 名 MCI 和 44 名 AD 痴呆患者）的回顾性探索队列。有关 Aβ42、Aβ40、t-Tau 和 p-Tau181 的基线 CSF 浓度的数据可用，并用于确定 AD 脑病理学的存在。使用高通量全自动 LUMIPULSE 测定法测定储存血浆样品中的基线 Aβ42、Aβ40 和 p-Tau181 浓度。在随访期间（平均 6.4 ± 2.5 年）评估了从 MCI 到 AD 痴呆的进展情况。此外，由 72 名患有记忆障碍的个体组成的前瞻性验证队列接受了 AD 生物标志物量化，这与典型的临床实践密切相关。该队列旨在证实该研究的主要发现。在探索性队列中，p-Tau181 的 CSF 和血浆之间的相关性中等（ρ = 0.61，p < 0.001），而 Aβ42/Aβ40 比率的相关性较弱（ρ = 0.39，p < 0.001）。在 AD 痴呆和前驱 AD 患者以及脑脊液淀粉样蛋白浓度异常 (A +) 的个体中，血浆 p-Tau181 和 p-Tau181/Aβ42 浓度显着升高，而 Aβ42/Aβ40 显着降低 (p < 0.001)。血浆 p-Tau181 在区分临床诊断为 AD 的患者方面表现出强大的性能（AUC = 0.89；95% CI 0.83–0.94）；A+ 与 A-（AUC = 0.84，95% CI 0.77–0.91）以及预测 MCI 患者转化为 AD 痴呆的结果（AUC = 0.89，95% CI 0.81–0.96）。在验证队列中进行测试时，根据淀粉样蛋白状态，血浆 p-Tau181 显示出总体一致性百分比的 83.3%。我们的结果表明，血浆中 p-Tau181 的测量作为一种在临床环境中实施的非侵入性预后筛查工具具有巨大的潜力。