# Clinical validation of Lumipulse G1200 automated immunoassays for Alzheimer's disease biomarkers in a Quebec cohort

## TL;DR

This study validates the Lumipulse G1200 immunoassays for detecting Alzheimer's disease biomarkers in blood and spinal fluid, showing strong agreement with PET scans in a Quebec cohort.

## Contribution

The study provides clinical validation of the Lumipulse G1200 immunoassays for Alzheimer's disease biomarkers in a real-world population.

## Key findings

- Plasma p-tau217 strongly correlates with amyloid and tau PET scans and outperforms p-tau181 in detecting tau pathology.
- Lumipulse G1200 immunoassays show high diagnostic accuracy for Alzheimer's disease biomarkers in both plasma and CSF.
- Plasma p-tau217 performs similarly to CSF p-tau181 in predicting amyloid and tau PET positivity.

## Abstract

With the anticipated arrival of disease‐modifying treatments for Alzheimer's disease (AD) in Canada, integrating biomarkers into clinical practice is crucial to enhancing diagnostic accuracy and optimizing referrals for treatment. Lumipulse G1200 (Fujirebio) is a fully automated immunoassay instrument that streamlines the analysis of these biomarkers. In this study, we evaluated the diagnostic performance of Lumipulse G1200 plasma and CSF immunoassays in detecting AD pathology within a Quebec population cohort.

Plasma and CSF samples of 102 participants from the TRIAD cohort (median age 67 years, 54% female) were analysed. Kruskal‐Wallis with post hoc Benjamini‐Hochberg false discovery rate (BH) correction compared the levels of biomarkers among the diagnostic groups. Discriminative performance for Aβ (18F‐NAV4694) and tau (18F‐MK6240) PET status was assessed using the area under the curve (AUC) of receiver operating characteristic (ROC). Amyloid PET global SUVR > 1.55 and tau PET metaROI SUVR>2.5STD of the young controls determined Aβ and Tau PET positivity, respectively. Spearman's correlation examined the association between plasma p‐tau217 and p‐tau181 with amyloid and tau PET SUVR.

Plasma p‐tau181 and p‐tau217 were higher in individuals with clinical diagnosis of AD compared to the cognitively unimpaired (CU) or MCI not due to AD (MCI‐). Plasma p‐tau217 very strongly correlated with both Aβ and tau PET SUVR (ρ=0.805 and 0.797 respectively, p‐value<2.2e‐16), as compared to plasma p‐tau181 (ρ=0.629 and 0.644 respectively, p < 4.097e‐10). Both assays identified with comparable high accuracy elevated Aβ pathology (plasma p‐tau217, AUC, 0.96, 95% CI: 0.92‐1.00; p‐tau181, AUC 0.88, CI 0.81‐ 0.96). However, plasma p‐tau217 had higher discriminative performance than p‐tau181 for tau PET (p‐tau217, AUC 0.99, CI: 0.98‐1.00; p‐tau181, AUC 0.94, CI 0.89‐0.98, DeLong's test p‐value<0.01). CSF p‐tau181, p‐tau181/Aβ42 and Aβ42/40 had excellent discriminative performance for Aβ and tau PET positivity. Moreover, plasma p‐tau217 had similar performance as CSF p‐tau181 for predicting Aβ and tau PET positivity.

Lumipulse G1200 immunoassays showed excellent agreement with amyloid and tau PET. Their ease of use and high diagnostic accuracy make them strong candidates for clinical implementation.