Keshavan Ashvini, Wellington Henrietta, Chen Zhongbo, Khatun Ayesha, Chapman Miles, Hart Melanie, Cash David M, Coath William, Parker Thomas D, Buchanan Sarah M, Keuss Sarah E, Harris Matthew J, Murray-Smith Heidi, Heslegrave Amanda, Fox Nick C, Zetterberg Henrik, Schott Jonathan M
Dementia Research Centre UCL Queen Square Institute of Neurology, University College London London UK.
UK Dementia Research Institute Fluid Biomarkers Laboratory UK DRI at University College London London UK.
Alzheimers Dement (Amst). 2021 Feb 6;13(1):e12131. doi: 10.1002/dad2.12131. eCollection 2021.
INTRODUCTION: We 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). METHODS: In 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 F-florbetapir amyloid PET status (n = 63). RESULTS: Measurements of CSF Aβ, p-tau181, and their ratios correlated well across platforms (r 0.84 to 0.94, < .0001); those of t-tau and t-tau/Aβ42 correlated moderately (r 0.57 to 0.79, < .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. DISCUSSION: The Lumipulse platform provides comparable sensitivity and specificity to established CSF immunoassays in identifying pre-symptomatic AD pathology.
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