[Consistency evaluation of the domestic Lifotronic platform and foreign luminescence platforms in detecting core cerebrospinal fluid biomarkers in Chinese Alzheimer disease patients].

Objective

To evaluate the consistency of measurement results and diagnostic agreement of core cerebrospinal fluid (CSF) biomarkers for Alzheimer disease (AD) in a Chinese population, which were measured across a domestically developed electrochemiluminescence platform (Lifotronic eCL8000), a Japanese chemiluminescence immunoassay platform (LUMIPULSE), and an American electrochemiluminescence platform (Meso Scale Discovery, MSD).

Methods

CSF samples were retrospectively collected from 253 subjects recruited at Peking Union Medical College Hospital, Xuanwu Hospital Capital Medical University, and Beijing Tiantan Hospital between July 2013 and September 2019. The cohort was comprised of 132 males and 121 females, with the age of (62.4±13.3) years. All CSF samples were collected via standardized protocols and cryopreserved at -80 ℃. Inter-assay repeatability (coefficient of variation, CV) of the Lifotronic platform on different days was validated. Spearman's rank correlation analysis was used to evaluate the degree of correlation between the results of the Pumen platform and those of the LUMIPULSE and MSD platforms, with the correlation coefficient expressed as ρ. Subsequently, 4 core CSF biomarkers [β-amyloid 40 (Aβ40), β-amyloid 42 (Aβ42), phosphorylated tau (p-tau), and total tau (t-tau)] were quantitatively measured across the three platforms. The consistency of test results between platforms was evaluated using the Passing-Bablok regression model and Bland-Altman analysis. The 95% limits of agreement (LoA) were calculated by Bland-Altman analysis, with good agreement indicated when <5% of points fell outside the limits. Proportional and constant errors between the measurement systems were quantified by the Passing-Bablok regression model, utilizing a robust non-parametric method. 18F-florbetapir positron emission tomography/positron emission tomography/computed tomography (PET/CT) imaging has been performed on 40 of the 253 subjects. With the PET/CT diagnostic results utilized as the gold standard, the diagnostic agreement between the CSF results from the 3 platforms and the PET/CT findings was compared by calculating Cohen's Kappa coefficient. Furthermore, AD diagnostic reference cut-off values for each platform were determined by employing receiver operating characteristic (ROC) curves.

Results

The Lifotronic platform demonstrated good repeatability in CSF testing (CV<10%). Spearman's rank correlation analysis was used to evaluate the correlation between the Lifotronic platform and the LUMIPULSE and MSD platforms, with correlation coefficients denoted by ρ. In comparison with the LUMIPULSE platform, all correlation coefficients (ρ) were>0.85. The correlation coefficient (ρ) between the MSD and Lifotronic platforms was>0.80, with a Kappa value of 0.698 (P<0.05). Bland-Altman analysis and Passing-Bablok regression models showed that for t-tau, the mean bias between Lifotronic and LUMIPULSE was 214.95 (95%LoA:-1 490.59-1 920.50), with 99.60% (252/253) of the data points falling within the 95%LoA. In the detection of t-tau, the regression slope between the Lifotronic and LUMIPULSE platforms was 2.041 (Equation: Y=2.041X-75.184), and the regression slope with the MSD platform was 2.360 (Equation: Y=2.360X-87.503). Based on PET/CT imaging validation, the CSF diagnostic results of the Lifotronic platform were consistent with the PET/CT results (Kappa=0.885, P<0.05), as were those of the MSD platform (Kappa=0.714, P<0.05). The Lifotronic platform established AD diagnostic reference thresholds based on the t-tau/Aβ42 and p-tau-181/Aβ42 ratios (the cut-off value for t-tau/Aβ42 was 0.32, and for p-tau-181/Aβ42 was 0.035). The Kappa value between the Lifotronic and LUMIPULSE platforms was 0.928 (P<0.05), and the Kappa value between the Lifotronic and MSD platforms was 0.698 (P<0.05).

Conclusion

This study systematically validated the reliability of domestically developed Lifotronic electrochemiluminescence platform and its corresponding assay kits in detecting AD CSF biomarkers, as well as their comparability with international platforms, demonstrating comparable capabilities in terms of accuracy, consistency, and cost control.