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 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 beta-amyloid (A beta) 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 beta-PET, and 143 without CSFs). Three annual cognitive and neuropsychiatric function tests were conducted. A beta 42, A beta 40, total-tau, and phosphorylated-tau(181) 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 beta-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 beta-PET status in a subgroup without CSF (n = 143), and then when we applied CSF biomarker cutoffs determined based on the A beta-PET status, the CSF biomarkers (cutoffs of 642.1 pg/mL for A beta 42, 0.060 for A beta 42/A beta 40, 0.315 for t-tau/A beta 42, and 0.051 for p-tau/A beta 42, respectively) showed good agreement with A beta-PET (overall AUC ranges of 0.840-0.898). Use of the A beta-PET-based CSF cutoffs showed excellent diagnostic discrimination between AD and CN (A beta 42, A beta 42/A beta 40, t-tau/A beta 42, and p-tau/A beta 42) with overall AUC ranges of 0.876-0.952. During follow-up, participants with AD-like CSF signature determined by A beta-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 beta-PET in Koreans. The Korean-specific A beta-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.