Analytical performance overview of the Lumipulse G pTau 181 Plasma RUO

Abstract Background Studies have shown that changes in Alzheimer’s disease (AD) biomarker levels occur in blood at approximately the same time as in cerebrospinal fluid (CSF). Therefore, plasma‐based testing could be used as a simple, accessible, and scalable approach to help support the diagnosis of AD, avoiding the complexity of CSF sampling, and the high costs and limited availability of PET imaging. It was demonstrated that plasma pTau181 has the potential to be a good predictor of amyloid PET positivity, has proven to differentiate between AD and non‐AD neurodegenerative diseases, and is able to predict progression to AD. The aim of this study was to determine the preliminary analytical performance of the newly developed Lumipulse G pTau 181 Plasma RUO assay. Method The LUMIPULSE G System is a chemiluminescent enzyme immunoassay platform that allows fully automated processing of samples using ready‐to‐use immunoreaction cartridges. Time to result in these single use test cartridges takes about 30 minutes. The assay uses AT270 for capturing and HT7/BT2‐conjugate for detection in a 2‐step set‐up. Parameters analysed were precision, sensitivity, linearity, and potential impact of interfering substances. The studies included a series of buffer– and K 2 EDTA plasma samples at different concentration levels, each tested in several replicates sized to the different parameters tested. Result The total within‐lab variability of the assay was found to be <5% CV for each of the samples tested, confirming the high precision of the LUMIPULSE G platform. Using low pTau181 concentrated plasma samples, the LoD was found to be <0.20 pg/mL, and the LoQ <0.50 pg/mL. The high sensitivity was confirmed by a formal concentration assignment to each tested samples of a cohort of healthy elderly subjects. Linearity was shown across the measurement range of the assay (0 – 60 pg/mL), and no significant impact of rheumatoid factor and human anti‐mouse antibodies was observed. Conclusion This preliminary verification of the analytical performance of the Lumipulse G pTau 181 Plasma RUO indicated promising results in terms of low variability, good dilutional linearity, and high sensitivity. The assay is now ready for full analytical verification and clinical validation towards the identified contexts of use.