Correspondence of CSF biomarkers measured by Lumipulse assays with amyloid PET

Abstract

AbstractBackgroundTraditional plate‐based assays for cerebrospinal fluid (CSF) biomarkers have been limited by relatively high assay variance that reduces the accuracy of individual measurements. Next generation automated assay platforms for CSF biomarkers reduce the variability of measurements, including across sample runs. In the current study, we utilized the Lumipulse G1200 (Fujirebio; Malvern, PA), a fully‐automated assay platform to compare CSF biomarkers to brain amyloid burden as determined by positron emission tomography (PET) imaging.MethodParticipants (n=758) were enrolled in studies of memory and aging at the Knight ADRC in St. Louis, Missouri. Concentrations of CSF amyloid‐beta 40 (Aβ40), amyloid‐beta 42 (Aβ42), total tau (tTau) and phosphorylated tau‐181 (pTau) were measured using the Lumipulse G1200 automated assay system. Brain amyloid burden was measured via amyloid PET imaging using Florbetapir or Pittsburgh compound B (PIB). The correspondence of CSF biomarkers with amyloid PET status based on established cut‐offs for each radiotracer was evaluated.ResultFor pooled CSF controls representing a range of three values (low, medium, high), coefficients for inter‐day variability ranged from 2‐4%. CSF collected within two years of an amyloid PET scan was evaluated from 521 amyloid PET‐negative and 237 amyloid PET‐positive individuals. Correspondence with amyloid PET by receiver operating characteristic (ROC) area under the curve (AUC) was highest for ratios including Aβ42: pTau/Aβ42 (0.97, 95% confidence intervals 0.96‐0.99), Aβ42/Aβ40 (0.97, 0.95‐0.98), and tTau/Aβ42 (0.96, 0.94‐0.97). A CSF pTau/Aβ42 value of >0.0649 had the highest combined positive and negative percent agreement (PPA of 0.91, 0.86‐0.94; NPA of 0.96, 0.93‐0.97) with amyloid PET status. The CSF value for Aβ42/Aβ40 with highest combined PPA and NPA was slightly more sensitive but less specific: <0.0673 had a PPA of 0.97 (0.94‐0.99) and NPA of 0.91 (0.88‐0.93) with amyloid PET status.ConclusionMeasurement of CSF biomarkers with the Lumipulse G1200 automated assay system was highly precise, with low variability over multiple runs. Values for pTau/Aβ42, Aβ42/Aβ40, and tTau/Aβ42 were highly concordant with amyloid PET status.