Lumipulse® pTau-217/Beta Amyloid 42 Ratio: Reactivation Summary

The Lumipulse® pTau-217/Beta Amyloid 42 Ratio is an in vitro diagnostic (IVD) assay intended to support the identification of amyloid pathology associated with Alzheimer’s disease. Following a manufacturer-identified reagent issue in December 2025, the assay was temporarily withdrawn from clinical use.

In April 2026, the manufacturer confirmed corrective actions and re-established compliance with U.S. Food and Drug Administration (FDA) performance standards. Following receipt of newly manufactured reagent lots, Labcorp performed an independent requalification and validation study to confirm assay performance prior to reinstatement.

Requalification and analytical validation summary

Labcorp evaluated analytical performance across four key domains: precision, accuracy, linearity, and inter-assay reproducibility. Additionally, Labcorp performed a clinical validity study. 

Results demonstrated that all analytical performance characteristics met established industry criteria for IVD assays. Importantly, clinical validation using an established cohort with amyloid PET-confirmed pathology was confirmed by concordance between the amyloid PET status and amyloid status set by the IVD assay cut-offs, with >90% accuracy. These data support the reinstatement of the Lumipulse pTau-217/ Beta Amyloid 42 Ratio assay for clinical use. These observations indicate that the corrective actions implemented by the manufacturer were effective and that assay integrity has been restored. Consistent with our internal protocols, Labcorp will perform ongoing monitoring of reagent lot consistency to confirm sustained, appropriate assay performance over time.

Materials and methods

Precision

Assay precision is the agreement between multiple measures of a sample given unchanged conditions. It is also known as repeatability when identical samples are analyzed within the same run (intra-assay precision), and inter-assay precision if identical samples are analyzed across different runs, typically between days. Precision is measured by looking at the standard deviation (SD) or coefficient of variation (%CV) in the results of each analyte and the ratio of the concentrations. 

Precision (repeatability and inter-assay precision) was assessed using four samples tested in quintuplicate over five consecutive days. Variability was quantified using SD and %CV for individual analytes and the calculated ratio. 

Results: All tested samples demonstrated %CV values within established acceptance criteria for IVD assays, indicating robust repeatability within assay runs and inter-assay precision across days and replicates.

Accuracy

Accuracy is the ability of the assay to detect and measure the true values of what is present in a sample. This is accomplished by determining the agreement between a test result and an accepted reference value.  Several different approaches include successful detection of the expected level of known quantities of the added substance to be measured (spike-recovery), analysis of reference material of known concentration and comparison to expected values, and analysis by a reference method and achieving equivalent results.

Accuracy was evaluated through two complementary approaches:

• Analysis of manufacturer-provided reference materials, assessing percent recovery of known concentrations
  Results: Reference material testing demonstrated acceptable recovery across all analyte levels
• Analysis by a reference method: Cross-site comparison, whereby identical sample sets were analyzed both internally and at the manufacturer’s reference laboratory.
  Results: Cross-site comparison confirmed equivalence between internal laboratory results and manufacturer-generated data, supporting analytical accuracy

Linearity

Linearity is an assay's ability to measure results correctly as the concentration of the measurable analyte increases. In simple terms, as the concentration increases, the results should respond in kind, producing a linear plot of concentration versus results. This is to confirm that the instrument’s calibration is correct. Linearity is measured in slope and percent bias (%bias), which is the degree to which the slope deviates from 1.0. 

Linearity was assessed by analyzing samples across a range of concentrations to evaluate proportional assay response. Performance was quantified using slope and %bias relative to expected values. 

Results: Linearity studies showed slopes approximating unity, with minimal %bias across the analytical measurement range, confirming appropriate assay calibration and response proportionality.

Inter-assay reproducibility (intermediate precision)

Reproducibility, more specifically, intermediate precision across varying conditions (instrument, operator) was assessed using %CV to measure variability across independent runs. 

Results: An intermediate precision study demonstrated low %CV values across different instruments and operators, indicating consistent assay performance.

Clinical validation

Clinical performance was evaluated using an intent-to-treat (ITT) cohort derived from the Australian Imaging, Biomarker and Lifestyle (AIBL) study. Amyloid PET imaging served as the reference standard to assess concordance with IVD determined amyloid categories (negative, indeterminant, positive defined by IVD cut-offs). Sensitivity, specificity, predictive values, and accuracy were assessed using established statistical methods consistent with prior published work (Doecke et al, 2025).

Results: Analysis of the AIBL ITT cohort demonstrated performance characteristics consistent with previously published data. Diagnostic accuracy and other measures for detecting amyloid pathology remained stable relative to historical benchmarks, confirming preservation of clinical utility with the new reagent lots.