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Alzheimer's Research & Therapy
Published in: Alzheimer's Research & Therapy 1/2021

Open Access 01-12-2021 | Alzheimer's Disease | Research

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

Authors: Sohee Moon, Sujin Kim, Sakulrat Mankhong, Seong Hye Choi, Manu Vandijck, Vesna Kostanjevecki, Jee Hyang Jeong, Soo Jin Yoon, Kyung Won Park, Eun-Joo Kim, Bora Yoon, Hee Jin Kim, Jae-Won Jang, Jin Yong Hong, Dong-Ho Park, Leslie M. Shaw, Ju-Hee Kang

Published in: Alzheimer's Research & Therapy | Issue 1/2021

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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 β-amyloid (Aβ) 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 Aβ-PET, and 143 without CSFs). Three annual cognitive and neuropsychiatric function tests were conducted. Aβ42, Aβ40, 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 Aβ-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 Aβ-PET status in a subgroup without CSF (n = 143), and then when we applied CSF biomarker cutoffs determined based on the Aβ-PET status, the CSF biomarkers (cutoffs of 642.1 pg/mL for Aβ42, 0.060 for Aβ42/Aβ40, 0.315 for t-tau/Aβ42, and 0.051 for p-tau/Aβ42, respectively) showed good agreement with Aβ-PET (overall AUC ranges of 0.840–0.898). Use of the Aβ-PET-based CSF cutoffs showed excellent diagnostic discrimination between AD and CN (Aβ42, Aβ42/Aβ40, t-tau/Aβ42, and p-tau/Aβ42) with overall AUC ranges of 0.876–0.952. During follow-up, participants with AD-like CSF signature determined by Aβ-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 Aβ-PET in Koreans. The Korean-specific Aβ-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.
Appendix
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Metadata
Title
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
Authors
Sohee Moon
Sujin Kim
Sakulrat Mankhong
Seong Hye Choi
Manu Vandijck
Vesna Kostanjevecki
Jee Hyang Jeong
Soo Jin Yoon
Kyung Won Park
Eun-Joo Kim
Bora Yoon
Hee Jin Kim
Jae-Won Jang
Jin Yong Hong
Dong-Ho Park
Leslie M. Shaw
Ju-Hee Kang
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 1/2021
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/s13195-020-00767-3

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