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. 2022 Oct 21;10(10):2667.
doi: 10.3390/biomedicines10102667.

A Novel Automated Chemiluminescence Method for Detecting Cerebrospinal Fluid Amyloid-Beta 1-42 and 1-40, Total Tau and Phosphorylated-Tau: Implications for Improving Diagnostic Performance in Alzheimer's Disease

Marina Arcaro  1 , Chiara Fenoglio  2 , Maria Serpente  1 , Andrea Arighi  1 , Giorgio G Fumagalli  1 , Luca Sacchi  3 , Stefano Floro  1   3 , Marianna D'Anca  1 , Federica Sorrentino  3 , Caterina Visconte  3 , Alberto Perego  4 , Elio Scarpini  1   3 , Daniela Galimberti  1   3
Affiliations

A Novel Automated Chemiluminescence Method for Detecting Cerebrospinal Fluid Amyloid-Beta 1-42 and 1-40, Total Tau and Phosphorylated-Tau: Implications for Improving Diagnostic Performance in Alzheimer's Disease

Marina Arcaro et al. Biomedicines. .

Abstract

Recently, a fully automated instrument for the detection of the Cerebrospinal Fluid (CSF) biomarker for Alzheimer’s disease (AD) (low concentration of Amyloid-beta 42 (Aβ42), high concentration of total tau (T-tau) and Phosphorylated-tau (P-tau181)), has been implemented, namely CLEIA. We conducted a comparative analysis between ELISA and CLEIA methods in order to evaluate the analytical precision and the diagnostic performance of the novel CLEIA system on 111 CSF samples. Results confirmed a robust correlation between ELISA and CLEIA methods, with an improvement of the accuracy with the new CLEIA methodology in the detection of the single biomarkers and in their ratio values. For Aβ42 regression analysis with Passing−Bablok showed a Pearson correlation coefficient r = 0.867 (0.8120; 0.907% 95% CI p < 0.0001), T-tau analysis: r = 0.968 (0.954; 0.978% 95% CI p < 0.0001) and P-tau181: r = 0.946 (0.922; 0.962 5% 95% CI p < 0.0001). The overall ROC AUC comparison between ROC in ELISA and ROC in CLEIA confirmed a more accurate ROC AUC with the new automatic method: T-tau AUC ELISA = 0.94 (95% CI 0.89; 0.99 p < 0.0001) vs. AUC CLEIA = 0.95 (95% CI 0.89; 1.00 p < 0.0001), and P-tau181 AUC ELISA = 0.91 (95% CI 0.85; 0.98 p < 0.0001) vs. AUC CLEIA = 0.98 (95% CI 0.95; 1.00 p < 0.0001). The performance of the new CLEIA method in automation is comparable and, for tau and P-tau181, even better, as compared with standard ELISA. Hopefully, in the future, automation could be useful in clinical diagnosis and also in the context of clinical studies.

Keywords: Alzheimer’s disease; CLEIA; CSF; ELISA; biomarkers.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Correlation analysis by non-parametric Passing–Bablok regression for method comparison between classical manual ELISA and Lumipulse assay for all 111 subjects: (A) Aβ42, (B) T-tau, (C) P-tau181.
Figure 1
Figure 1
Correlation analysis by non-parametric Passing–Bablok regression for method comparison between classical manual ELISA and Lumipulse assay for all 111 subjects: (A) Aβ42, (B) T-tau, (C) P-tau181.
Figure 2
Figure 2
Receiver operating characteristic (ROC) curves to distinguish between AD patients and controls: (A) AUC analysis for ELISA Aβ42, T-tau and P-tau181 (B) AUC analysis for CLEIA Aβ42, Aβ42/Aβ40, T-tau and P-tau181, (C) AUC analysis for ratio T-tau/Aβ42 and P-tau181/Aβ42.
Figure 2
Figure 2
Receiver operating characteristic (ROC) curves to distinguish between AD patients and controls: (A) AUC analysis for ELISA Aβ42, T-tau and P-tau181 (B) AUC analysis for CLEIA Aβ42, Aβ42/Aβ40, T-tau and P-tau181, (C) AUC analysis for ratio T-tau/Aβ42 and P-tau181/Aβ42.
See this image and copyright information in PMC

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