Catania Marcella, Battipaglia Claudia, Perego Alberto, Salvi Erika, Maderna Emanuela, Cazzaniga Federico Angelo, Rossini Paolo M, Marra Camillo, Vanacore Nicola, Redolfi Alberto, Perani Daniela, Spadin Patrizia, Cotelli Maria, Cappa Stefano, Caraglia Naike, Tiraboschi Pietro, Tagliavini Fabrizio, Di Fede Giuseppe
Neurology 5 - Neuropathology Unit, Fondazione IRCCS - Istituto Neurologico Carlo Besta, Via Celoria 11, Milan, 20133, Italy.
Fujirebio Italia S.r.l, Via Pontina Km 29, Pomezia, Roma, 00071, Italy.
Fluids Barriers CNS. 2025 Jan 21;22(1):9. doi: 10.1186/s12987-025-00620-5.
The approval of new disease-modifying therapies by the U.S. Food and Drug Administration and the European Medicine Agency makes it necessary to optimize non-invasive and cost-effective tools for the identification of subjects at-risk of developing Alzheimer's Disease (AD). Plasma biomarkers are excellent candidates. However, their ability to reflect the cerebrospinal fluid (CSF) profile - that remains to date the gold standard for the biochemical diagnosis of AD - needs to be confirmed and validated before their implementation in clinical practice. The aims of this study are to analyse the correlation between CSF and plasma Aβ40, Aβ42, Aβ42/Aβ40 and pTau181, and to assess the diagnostic performance of plasma biomarkers in a cohort of subjects affected by Mild Cognitive Impairment (MCI).
The study was performed on 306 subjects affected by MCI, enrolled in the context of the Italian Interceptor Project. Aβ40, Aβ42 and pTau181 were analysed in plasma and CSF, and pTau217 was measured in plasma. The fully automated chemiluminescence enzyme immunoassay and the Lumipulse G600II (Fujirebio) instrument were used for all measurements. We analysed the correlations between CSF and plasma biomarkers and the differences of plasma biomarker concentrations after grouping MCI cases according to AT classification of CSF AD biomarker profiles.
We found statistically significant positive correlations between CSF and plasma Aβ42, Aβ42/Aβ40 ratio and pTau181. All the biomarkers, except Aβ40, showed differences in A+ vs. A-, A+T+ vs. A-T- and A+T- vs. A-T- patients. Moreover, Aβ42 and Aβ42/Aβ40 plasma levels were lower in A+T- compared to A-T- and A-T+ groups, and pTau181 and pTau217 plasma levels were higher in A+T+ compared to A+T-. Aβ42/Aβ40 and pTau217 showed a robust performance in distinguishing A+ from A- (AUC = 0.857 and 0.862, respectively) and A+T+ from A-T- (AUC = 0.866 and 0.911) subjects.
Our results suggest that plasma biomarkers, and especially Aβ42/Aβ40 ratio and pTau217, are promising candidates for the early detection of AD pathology.
美国食品药品监督管理局和欧洲药品管理局批准了新的疾病修饰疗法，因此有必要优化用于识别有患阿尔茨海默病（AD）风险个体的非侵入性且具有成本效益的工具。血浆生物标志物是很好的候选者。然而，它们反映脑脊液（CSF）特征的能力——脑脊液仍是迄今为止AD生化诊断的金标准——在临床实践应用之前需要得到确认和验证。本研究的目的是分析脑脊液与血浆中Aβ40、Aβ42、Aβ42/Aβ40和pTau181之间的相关性，并评估血浆生物标志物在一组轻度认知障碍（MCI）患者中的诊断性能。
该研究对306名MCI患者进行，这些患者纳入了意大利拦截器项目。对血浆和脑脊液中的Aβ40、Aβ42和pTau181进行分析，并检测血浆中的pTau217。所有测量均使用全自动化学发光酶免疫测定法和Lumipulse G600II（富士瑞必欧）仪器。我们分析了脑脊液与血浆生物标志物之间的相关性，以及根据脑脊液AD生物标志物谱的AT分类对MCI病例进行分组后血浆生物标志物浓度的差异。
我们发现脑脊液与血浆中的Aβ42、Aβ42/Aβ40比值和pTau181之间存在统计学上显著的正相关。除Aβ40外，所有生物标志物在A+与A-、A+T+与A-T-以及A+T-与A-T-患者之间均显示出差异。此外，与A-T-和A-T+组相比，A+T-组的血浆Aβ42和Aβ42/Aβ40水平较低，与A+T-组相比，A+T+组的血浆pTau181和pTau217水平较高。Aβ42/Aβ40和pTau217在区分A+与A-（AUC分别为0.857和0.862）以及A+T+与A-T-（AUC分别为0.866和0.911）个体方面表现出强大的性能。
我们的结果表明，血浆生物标志物，尤其是Aβ42/Aβ40比值和pTau217，是AD病理学早期检测的有前景的候选者。
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