Concordance of CSF measures of Alzheimer's pathology with amyloid PET status in a preclinical cohort: A comparison of Lumipulse and established immunoassays
Ashvini Keshavan, Henrietta Wellington, Zhongbo Chen, Ayesha Khatun, Miles Chapman, Melanie Hart, David M. Cash, William Coath, Thomas D. Parker, Sarah M. Buchanan, Sarah E Keuss, Matthew Harris, Heidi Murray‐Smith, Amanda Heslegrave, Nick C. Fox, Henrik Zetterberg, Jonathan M. Schott
Abstract
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 were derived. Logistic regressions and receiver-operating characteristic analysis generated CSF cut-points optimizing concordance with 18F-florbetapir amyloid PET status (n = 63). Results Measurements of CSF Aβ, p-tau181, and their ratios correlated well across platforms (r 0.84-.94, P < .0001); those of t-tau and t-tau/Aβ42 correlated moderately (r 0.57-0.79, P < .0001). The best concordance with amyloid PET (100% sensitivity and 94% specificity) was afforded by cut-points of 0.110 for Lumipulse Aβ42/Aβ40, 0.087 for MSD Aβ42/Aβ40, and 25.3 for Lumipulse Aβ42/p-tau181. Discussion The Lumipulse platform provides comparable sensitivity and specificity to established CSF immunoassays in identifying pre-symptomatic AD pathology.