Abstract
INTRODUCTIONWe assessed the concordance of cerebrospinal fluid (CSF) amyloid beta (Aβ) and tau measured on the fully automated Lumipulse platform with pre‐symptomatic Alzheimer's disease (AD) pathology on amyloid positron emission tomography (PET).METHODSIn 72 individuals from the Insight 46 study, CSF Aβ40, Aβ42, total tau (t‐tau), and phosphorylated tau at site 181 (p‐tau181) were measured using Lumipulse, INNOTEST, and Meso Scale Discovery (MSD) assays and inter‐platform Pearson correlations derived. Lumipulse Aβ42 measures were adjusted to incorporate standardization to certified reference materials. Logistic regressions and receiver operating characteristics analysis generated CSF cut‐points optimizing concordance with 18F‐florbetapir amyloid PET status (n = 63).RESULTSMeasurements of CSF Aβ, p‐tau181, and their ratios correlated well across platforms (r 0.84 to 0.94, P < .0001); those of t‐tau and t‐tau/Aβ42 correlated moderately (r 0.57 to 0.79, P < .0001). The best concordance with amyloid PET (100% sensitivity and 94% specificity) was afforded by cut‐points of 0.075 for Lumipulse Aβ42/Aβ40, 0.087 for MSD Aβ42/Aβ40 and 17.3 for Lumipulse Aβ42/p‐tau181.DISCUSSIONThe Lumipulse platform provides comparable sensitivity and specificity to established CSF immunoassays in identifying pre‐symptomatic AD pathology.
Highlights
We assessed the concordance of cerebrospinal fluid (CSF) amyloid beta (Aβ) and tau measured on the fully automated Lumipulse platform with presymptomatic Alzheimer’s disease (AD) pathology on amyloid positron emission tomography (PET)
In the present study we extend the comparison of individual Lumipulse CSF Aβ40, Aβ42, t-tau, and p-tau[181] markers to include ratios, with direct comparison to the INNOTEST and Meso Scale Discovery (MSD) platforms
In this study we build on previous validations of Lumipulse measurements of CSF amyloid β (Aβ) and tau biomarkers against two other established CSF assay platforms
Summary
Cerebrospinal fluid (CSF) amyloid beta (Aβ) and tau, and quantification of cortical amyloid burden by positron emission tomography (PET) remain among the best-established biomarkers of Alzheimer’s disease (AD). There is a drive toward validating fully automated platforms that reduce manual steps as a source for variation One of these automated platforms is the Lumipulse G system (Fujirebio), on which chemiluminescent immunoassays for Aβ40, Aβ42, t-tau, and p-tau[181] have been developed, using the same antibodies as the INNOTEST ELISAs. Recent studies directly comparing measurements by Lumipulse with INNOTEST ELISAs have shown good concordance between the two platforms but reduced intra- and inter-assay variability on the Lumipulse.[18,19,20,21,22] systematic differences in absolute CSF Aβ42 concentrations between Lumipulse and INNOTEST platforms have been observed,[18,19] with one study reporting 27% lower concentrations measured by INNOTEST compared to Lumipulse.[18] When assessing the diagnostic accuracy of Lumipulse CSF Aβ and tau in classifying individuals with clinical AD from cognitively normal controls, Lumipulse ratios of Aβ42/Aβ40, Aβ42/t-tau, and Aβ42/p-tau[181] were found to have a higher diagnostic accuracy than individual markers.[20,21]. We supplement existing knowledge about the possible contribution of Aβ40 interference to differences in measurements of Aβ42 by evaluating all three platforms, and assess concordance of individual markers and ratios with amyloid PET imaging in a preclinical cohort
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