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

Exploring the potential of fully automated LUMIPULSE G plasma assays for detecting Alzheimer's disease pathology.

机构信息

Faculty of Medicine, University of Coimbra, Coimbra, Portugal.

Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal.

出版信息

Alzheimers Res Ther. 2024 Mar 7;16(1):51. doi: 10.1186/s13195-024-01397-9.

DOI:10.1186/s13195-024-01397-9

PMID:38454502

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10918996/

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

背景

LUMIPULSE G-自动化免疫分析是一种广泛用于定量检测脑脊液（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志物为 AD 诊断的早期阶段（轻度认知障碍（MCI））提供了有希望的工具。用于定量检测血液中淀粉样蛋白-β（Aβ）和磷酸化 Tau-181（p-Tau181）的高灵敏度检测方法显示出有希望的结果。在这项研究中，我们评估了最近可用的全自动 LUMIPULSE 血浆标志物检测方法在检测大脑 AD 病理学和预测 MCI 向 AD 痴呆阶段进展方面的临床性能。

方法

纳入了 138 名个体的回顾性探索性队列（22 名神经科对照组[NC]、72 名 MCI 和 44 名 AD 痴呆患者）。基线时 CSF 中 Aβ42、Aβ40、t-Tau 和 p-Tau181 的浓度数据可用，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，从储存的血浆样本中测定基线 Aβ42、Aβ40 和 p-Tau181 浓度。在随访期间（平均 6.4±2.5 年）评估从 MCI 到 AD 痴呆的进展情况。此外，72 名有记忆主诉的个体进行了 AD 生物标志物定量检测，这与典型的临床实践非常相似。该队列旨在证实研究的主要发现。

结果

在探索性队列中，CSF 和血浆之间的相关性对于 p-Tau181 为中度（ρ=0.61，p<0.001），对于 Aβ42/Aβ40 比值为弱（ρ=0.39，p<0.001）。AD 痴呆和前驱 AD 患者以及 CSF 中淀粉样蛋白浓度异常（A+）患者的血浆 p-Tau181 和 p-Tau181/Aβ42 浓度显著升高，而 Aβ42/Aβ40 浓度显著降低（p<0.001）。血浆 p-Tau181 在区分临床诊断为 AD 的患者方面具有出色的性能（AUC=0.89；95%CI 0.83-0.94）；A+与 A-（AUC=0.84，95%CI 0.77-0.91），并且在预测 MCI 患者向 AD 痴呆的转化方面也具有良好的预测能力（AUC=0.89，95%CI 0.81-0.96）。当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 83.3%的总体符合率。