LUMIPULSE G® CSF AD BIOMARKER CONCORDANCE TO PET IN THE KBASE COHORT

Abstract

Accurate, reliable, and highly standardized measurement of cerebrospinal fluid (CSF) biomarker profiles in patients suspected to suffer from Alzheimer's Disease (AD), can help in setting correct diagnosis and enrichment of AD-drug clinical trials, as of early stages. Compared to Position Emission Tomography (PET) these measurements are relatively cheap and applicable on large scale. As part of an immunoassay platform comparison study, CSF samples of the Korean Brain Aging Study for the Early Diagnosis and Prediction of AD study (KBASE) were analyzed for the AD CSF core biomarkers on the LUMIPULSE G platform. Here we present cut-point determinations for the Lumipulse CSF biomarkers based on PET amyloid positivity. A total of 126 CSF samples of the KBASE study with known PET status (visual reading) were analyzed on the fully automated Lumipulse G AD biomarker panel (β-Amyloid 1–42 (CRM standardized), β-Amyloid 1-40, Total Tau, and pTau 181). For each individual analyte and ratio using Aβ1-42, a cut-point was determined using ROC curve analysis and Youden index. Concordance with amyloid PET was reported as Positive, Negative, and Overall Percentage Agreement (OPA). All samples were successfully analyzed on the LUMIPULSE G1200 instrument. For the 39 PET-positive and 87 PET-negative samples, analyte concentrations were within the assay's measurement range, except for 11 Total Tau measurements. Compared to other cohorts, Total Tau concentrations were found to be lower, impacting the study cut-point determination. For the ratios using Aβ1-42, the Positive Percentage Agreement was above or equal to 85%, whilst Negative Percentage Agreement was at least 89%, illustrating high concordance with PET dichotomous classification of amyloid status. Based on the results of this cohort, for each analyte (excluding Aβ1-40) and ratio using Aβ1-42, a cut-point was identified, which aligned well with amyloid PET status. The discriminatory capacity of single analyte concentrations was lower compared to that of a ratio (single analyte OPA > 75%; ratio OPA > 85%), confirming results of similar studies. Although additional independent studies are needed to further validate the clinical performance of the identified cut-points, they can be applied in the context of studies using the same set-up.