Keshavan Ashvini, Wellington Henrietta, Chen Zhongbo, Khatun Ayesha, Chapman Miles, Hart Melanie, Cash David M, Coath William, Parker Thomas D, Buchanan Sarah M, Keuss Sarah E, Harris Matthew J, Murray-Smith Heidi, Heslegrave Amanda, Fox Nick C, Zetterberg Henrik, Schott Jonathan M
Dementia Research Centre UCL Queen Square Institute of Neurology, University College London London UK.
UK Dementia Research Institute Fluid Biomarkers Laboratory UK DRI at University College London London UK.
Alzheimers Dement (Amst). 2021 Feb 6;13(1):e12131. doi: 10.1002/dad2.12131. eCollection 2021.
We assessed the concordance of cerebrospinal fluid (CSF) amyloid beta (Aβ) and tau measured on the fully automated Lumipulse platform with pre-symptomatic Alzheimer's disease (AD) pathology on amyloid positron emission tomography (PET).
In 72 individuals from the Insight 46 study, CSF Aβ40, Aβ42, total tau (t-tau), and phosphorylated tau at site 181 (p-tau181) were measured using Lumipulse, INNOTEST, and Meso Scale Discovery (MSD) assays and inter-platform Pearson correlations derived. Lumipulse Aβ42 measures were adjusted to incorporate standardization to certified reference materials. Logistic regressions and receiver operating characteristics analysis generated CSF cut-points optimizing concordance with F-florbetapir amyloid PET status (n = 63).
Measurements of CSF Aβ, p-tau181, and their ratios correlated well across platforms (r 0.84 to 0.94, < .0001); those of t-tau and t-tau/Aβ42 correlated moderately (r 0.57 to 0.79, < .0001). The best concordance with amyloid PET (100% sensitivity and 94% specificity) was afforded by cut-points of 0.075 for Lumipulse Aβ42/Aβ40, 0.087 for MSD Aβ42/Aβ40 and 17.3 for Lumipulse Aβ42/p-tau181.
The Lumipulse platform provides comparable sensitivity and specificity to established CSF immunoassays in identifying pre-symptomatic AD pathology.
我们评估了在全自动Lumipulse平台上测量的脑脊液（CSF）淀粉样蛋白β（Aβ）和tau与淀粉样蛋白正电子发射断层扫描（PET）上的症状前阿尔茨海默病（AD）病理的一致性。
在Insight 46研究的72名个体中，使用Lumipulse、INNOTEST和Meso Scale Discovery（MSD）检测法测量CSF Aβ40、Aβ42、总tau（t-tau）和第181位磷酸化tau（p-tau181），并得出平台间的Pearson相关性。对Lumipulse Aβ42测量值进行调整，以纳入对认证参考物质的标准化。逻辑回归和受试者工作特征分析生成了CSF切点，以优化与F-氟代硼吡咯淀粉样蛋白PET状态（n = 63）的一致性。
CSF Aβ、p-tau181及其比率的测量值在各平台间相关性良好（r = 0.84至0.94，P <.0001）；t-tau和t-tau/Aβ42的测量值相关性中等（r = 0.57至0.79，P <.0001）。Lumipulse Aβ42/Aβ40切点为0.075、MSD Aβ42/Aβ40切点为0.087以及Lumipulse Aβ42/p-tau181切点为17.3时，与淀粉样蛋白PET的一致性最佳（敏感性100%，特异性94%）。
在识别症状前AD病理方面，Lumipulse平台提供了与既定CSF免疫测定相当的敏感性和特异性。
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