Multivariate models using NULISAseq and plasma p-tau217 for staging Alzheimer's disease

Plasma phospho-tau217 (p-tau217) has been shown to demonstrate equal performance to cerebrospinal fluid (CSF) to predict amyloid beta (Aβ) positivity. Although such high-performing plasma tests provide confirmatory information on Aβ status, further information is desperately needed to discern optimal blood-based biomarkers (BBMs) across the Alzheimer's disease (AD) stage.

From the Australian Imaging, Biomarkers and Lifestyle study, 387 participants underwent [¹⁸F]NAV4694 (Aβ) and [¹⁸F]MK-6240 (tau) PET scans, a blood test to measure for p-tau217 (ALZpath and Lumipulse), and the Alamar Biosciences NULISASeq platform (120 central nervous system [CNS] and 250 inflammatory proteins). Individual p-tau217 assays were compared with selected biomarker sets from the Alamar panel to predict AD stage.

Using a panel of biomarkers was significantly better at predicting disease stage compared with p-tau217 alone; however, the difference was dependent upon p-tau217 assay.

Utility of extra BBMs in addition to p-tau217 provides useful information regarding overall disease burden during the separate stages of AD.

Of the separate assays for p-tau217, the Lumipulse assay demonstrated significantly better performance than the ALZpath assay to separate disease stages. Multivariate blood-based biomarker (BBM) models are significantly better at predicting the presence of A/T from A-T- as compared with any p-tau217 assay. Multivariate BBM models have higher area under the curve values to predict disease stage than Alamar and ALZpath p-tau217, but not Lumipulse p-tau217 during later disease stage comparisons.