Alzheimer’s Cerebrospinal Biomarkers from Lumipulse Fully Automated Immunoassay: Concordance with Amyloid-Beta PET and Manual Immunoassay in Koreans

Abstract Background: Universal Alzheimer’s disease (AD) cerebrospinal fluid (CSF) biomarker cutoffs from immunoassays with low interlaboratory variability could improve diagnostic accuracy and help predict disease progression. To determine the diagnostic cutoffs of CSF AD biomarkers measured with three immunoassay platforms, including fully automated Lumipulse based on b-amyloid (Ab) positron emission tomography (PET) status, to determine diagnostic utility and clinical predictability.Methods: Three hundred thirty-one Korean participants were 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: 71 cognitively normal (CN), 99 with subjective cognitive decline (SCD), 89 with mild cognitive impairment (MCI), and 72 with AD. Among these 331 participants, 139 (29, 58, 29, and 23 from each group, respectively) provided CSF and 271 underwent baseline amyloid PET. Three annual cognitive and neuropsychiatric function tests were conducted. Ab42, Ab40, 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 Ab-PET, were 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, and using the cutoffs for Ab-PET status with maximal AD diagnostic accuracy (n = 215), the levels showed excellent agreement with Ab-PET. Use of Ab-PET-based cutoffs for CSF biomarkers showed excellent diagnostic discrimination between AD and CN (Ab42, Ab42/Ab40, t-tau/Ab42 and p-tau/Ab42) with overall AUC ranges to discriminate AD and CN (0.876–0.952). During follow-up, participants with AD-like CSF signature determined by Ab-PET-based cutoffs from Lumipulse showed rapid progression of clinical scores, 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 Ab-PET. Ab-PET-based CSF biomarker cutoffs measured by immunoassays, including the Lumipulse, strongly predict progression of cognitive decline. The clinical utility of CSF biomarkers from fully automated immunoassay platforms should be evaluated in larger, more diverse cohorts.