Dataset Information

Alzheimer's cerebrospinal biomarkers from Lumipulse fully automated immunoassay: concordance with amyloid-beta PET and manual immunoassay in Koreans : CSF AD biomarkers measured by Lumipulse in Koreans.

ABSTRACT:

Background

Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarker cutoffs from immunoassays with low interlaboratory variability in diverse ethnic groups are necessary for their use in clinics and clinical trials. With lack of cutoffs from fully automated immunoassay platforms in diverse races, the aim of this study is to evaluate the clinical utility of CSF AD biomarkers from the Lumipulse fully automated immunoassay based on ?-amyloid (A?) positron emission tomography (PET) status comparing with these from two manual immunoassays, in Koreans.

Methods

Among 331 Korean participants enrolled from a prospective, 3-year longitudinal observational study of the validation cohort of Korean Brain Aging Study for the Early Diagnosis and Prediction of AD, 139 (29 CN, 58 SCD, 29 MCI, and 23 AD) provided CSF and 271 underwent baseline amyloid PET (n?=?128 with overlapping CSF and A?-PET, and 143 without CSFs). Three annual cognitive and neuropsychiatric function tests were conducted. A?42, A?40, total-tau, and phosphorylated-tau₁₈₁ were measured by Lumipulse fully automated immunoassay and two manual immunoassays (INNO-BIA AlzBio3, INNOTEST). Clinical utility of CSF biomarker cutoffs, based on 128 participants with A?-PET, was evaluated.

Results

Cognitive and neuropsychological scores differed significantly among the groups, with descending performance among CN>SCD>MCI>AD. Biomarker levels among immunoassays were strongly intercorrelated. We determined the A?-PET status in a subgroup without CSF (n?=?143), and then when we applied CSF biomarker cutoffs determined based on the A?-PET status, the CSF biomarkers (cutoffs of 642.1?pg/mL for A?42, 0.060 for A?42/A?40, 0.315 for t-tau/A?42, and 0.051 for p-tau/A?42, respectively) showed good agreement with A?-PET (overall AUC ranges of 0.840-0.898). Use of the A?-PET-based CSF cutoffs showed excellent diagnostic discrimination between AD and CN (A?42, A?42/A?40, t-tau/A?42, and p-tau/A?42) with overall AUC ranges of 0.876-0.952. During follow-up, participants with AD-like CSF signature determined by A?-PET-based cutoffs from Lumipulse showed rapid progression of cognitive decline in 139 subjects, after adjustment for potential confounders, compared with those with a normal CSF signature.

Conclusion

CSF AD biomarkers measured by different immunoassay platforms show strong intercorrelated agreement with A?-PET in Koreans. The Korean-specific A?-PET-based CSF biomarker cutoffs measured by the Lumipulse assay strongly predicts progression of cognitive decline. The clinical utility of CSF biomarkers from fully-automated immunoassay platforms should be evaluated in larger, more diverse cohorts.

SUBMITTER: Moon S

PROVIDER: S-EPMC7802266 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Alzheimer's cerebrospinal biomarkers from Lumipulse fully automated immunoassay: concordance with amyloid-beta PET and manual immunoassay in Koreans : CSF AD biomarkers measured by Lumipulse in Koreans.

Moon Sohee S Kim Sujin S Mankhong Sakulrat S Choi Seong Hye SH Vandijck Manu M Kostanjevecki Vesna V Jeong Jee Hyang JH Yoon Soo Jin SJ Park Kyung Won KW Kim Eun-Joo EJ Yoon Bora B Kim Hee Jin HJ Jang Jae-Won JW Hong Jin Yong JY Park Dong-Ho DH Shaw Leslie M LM Kang Ju-Hee JH

Alzheimer's research & therapy 20210112 1

<h4>Background</h4>Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarker cutoffs from immunoassays with low interlaboratory variability in diverse ethnic groups are necessary for their use in clinics and clinical trials. With lack of cutoffs from fully automated immunoassay platforms in diverse races, the aim of this study is to evaluate the clinical utility of CSF AD biomarkers from the Lumipulse fully automated immunoassay based on β-amyloid (Aβ) positron emission tomography (PET) statu ...[more]

PMID: 33436035

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Project description:Manual ELISA assays are the most commonly used methods for quantification of biomarkers; however, they often show inter- and intra-laboratory variability that limits their wide use. Here, we compared the Innotest ELISA method with two fully automated platforms (Lumipulse and Elecsys) to determine whether these new methods can provide effective substitutes for ELISA assays. We included 149 patients with AD (n = 34), MCI (n = 94) and non-AD dementias (n = 21). Aβ42, T-tau, and P-tau were quantified using the ELISA method (Innotest, Fujirebio Europe), CLEIA method on a Lumipulse G600II (Fujirebio Diagnostics), and ECLIA method on a Cobas e 601 (Roche Diagnostics) instrument. We found a high correlation between the three methods, although there were systematic differences between biomarker values measured by each method. Both Lumipulse and Elecsys methods were highly concordant with clinical diagnoses, and the combination of Lumipulse Aβ42 and P-tau had the highest discriminating power (AUC 0.915, 95% CI 0.822-1.000). We also assessed the agreement of AT(N) classification for each method with AD diagnosis. Although differences were not significant, the use of Aβ42/Aβ40 ratio instead of Aβ42 alone in AT(N) classification enhanced the diagnostic accuracy (AUC 0.798, 95% CI 0.649-0.947 vs. AUC 0.778, 95% CI 0.617-0.939). We determined the cut-offs for the Lumipulse and Elecsys assays based on the Aβ42/Aβ40 ratio ± status as a marker of amyloid pathology, and these cut-offs were consistent with those recommended by manufacturers, which had been determined based on visual amyloid PET imaging or diagnostic accuracy. Finally, the biomarker ratios (P-tau/Aβ42 and T-tau/Aβ42) were more consistent with the Aβ42/Aβ40 ratio for both Lumipulse and Elecsys methods, and Elecsys P-tau/Aβ42 had the highest consistency with amyloid pathology (AUC 0.994, 95% CI 0.986-1.000 and OPA 96.4%) at the ≥0.024 cut-off. The Lumipulse and Elecsys cerebrospinal fluid (CSF) AD assays showed high analytical and clinical performances. As both automated platforms were standardized for reference samples, their use is recommended for the measurement of CSF AD biomarkers compared with unstandardized manual methods, such as Innotest ELISA, that have demonstrated a high inter and intra-laboratory variability.

Dataset Information

Alzheimer's cerebrospinal biomarkers from Lumipulse fully automated immunoassay: concordance with amyloid-beta PET and manual immunoassay in Koreans : CSF AD biomarkers measured by Lumipulse in Koreans.

Background

Methods

Results

Conclusion

Publications

Alzheimer's cerebrospinal biomarkers from Lumipulse fully automated immunoassay: concordance with amyloid-beta PET and manual immunoassay in Koreans : CSF AD biomarkers measured by Lumipulse in Koreans.

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