Diagnostic accuracy of automated Lumipulse plasma pTau-217 in Alzheimer's disease: a real-world study.

BACKGROUND AND OBJECTIVES

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.

METHODS

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.

RESULTS

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.

DISCUSSION

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.