Neurology Unit, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy.
Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy.
J Neurol. 2024 Oct;271(10):6739-6749. doi: 10.1007/s00415-024-12631-7. Epub 2024 Aug 22.
This study evaluates the discriminative performance of the automated Lumipulse plasma pTau-217 compared to plasma pTau-181 and the Aβ42/Aβ40 ratio across cerebrospinal fluid (CSF) A/T classes and diagnostic groups within a memory-center-based population of cognitively impaired patients.
This cross-sectional study in a Memory Center enrolled 98 patients along the AD continuum or affected by other neurodegenerative disorders, stratified by CSF A/T status and clinical syndrome. Plasma pTau-217, pTau-181, and Aβ42/Aβ40 were measured using Lumipulse. Relationships with CSF and glomerular filtration rate (GFR) were explored. ROC analysis was conducted to assess diagnostic performance.
The CSF A/T profiles included 49 A+/T+, 8 A+/T-, and 41 A-/T-. Clinical diagnoses at discharge were AD-dementia (AD-DEM), AD-MCI, NonAD-MCI, and NonAD-dementia (NonAD-DEM). Plasma pTau-217 and the pTau-217/Aβ42 ratio strongly correlated with CSF pTau-181 and total Tau (R = 0.80). GFR had minimal influence on plasma biomarker ratios. Plasma pTau-217 exhibited excellent AUC values (0.94-0.97) for distinguishing CSF A+/T+ and A+ status, showing higher discriminative accuracy than pTau-181 and Aβ42/Aβ40 (AUCs: 0.66-0.83). Optimal cutoff for plasma pTau-217 indicated excellent accuracy (93.3%), sensitivity (91.8%), and specificity (95.1%). AD-DEM patients displayed the highest pTau-217 levels, with significant differences across clinical groups.
The findings confirm that Lumipulse plasma pTau-217 offers superior diagnostic accuracy for reflecting CSF A/T status. Plasma pTau-217 emerged as an accurate standalone biomarker of AD neuropathology across MCI and dementia stages. The study underscores the utility of automated Lumipulse assays, promoting their integration into routine diagnostic workflows to facilitate early and accurate AD detection.
本研究评估了 Lumipulse 血浆 pTau-217 相对于血浆 pTau-181 和 Aβ42/Aβ40 比值在基于记忆中心的认知障碍患者人群的脑脊液 (CSF) A/T 类别和诊断组中的鉴别性能。
这项在记忆中心进行的横断面研究共纳入了 98 名沿着 AD 连续体或受其他神经退行性疾病影响的患者，按 CSF A/T 状态和临床综合征分层。使用 Lumipulse 测量血浆 pTau-217、pTau-181 和 Aβ42/Aβ40。探索与 CSF 和肾小球滤过率 (GFR) 的关系。进行 ROC 分析以评估诊断性能。
CSF A/T 谱包括 49 例 A+/T+、8 例 A+/T-和 41 例 A-/T-。出院时的临床诊断为 AD 痴呆 (AD-DEM)、AD 认知障碍 (AD-MCI)、非 AD-MCI 和非 AD 痴呆 (NonAD-DEM)。血浆 pTau-217 和 pTau-217/Aβ42 比值与 CSF pTau-181 和总 Tau 呈强相关性 (R=0.80)。GFR 对血浆生物标志物比值的影响最小。血浆 pTau-217 在区分 CSF A+/T+和 A+状态方面具有出色的 AUC 值 (0.94-0.97)，显示出比 pTau-181 和 Aβ42/Aβ40 更高的鉴别准确性 (AUC：0.66-0.83)。血浆 pTau-217 的最佳截断值表明具有出色的准确性 (93.3%)、敏感性 (91.8%) 和特异性 (95.1%)。AD-DEM 患者显示出最高的 pTau-217 水平，在不同临床组之间存在显著差异。
研究结果证实，Lumipulse 血浆 pTau-217 提供了反映 CSF A/T 状态的更高诊断准确性。血浆 pTau-217 成为 MCI 和痴呆阶段 AD 神经病理学的准确独立生物标志物。该研究强调了自动化 Lumipulse 测定的实用性，促进了其整合到常规诊断工作流程中，以促进 AD 的早期和准确检测。
