@article{4fe97949553c4f5d93e43f4c32a53504,
title = "Concordance of Lumipulse cerebrospinal fluid t-tau/Aβ42 ratio with amyloid PET status",
abstract = "Introduction: Cerebrospinal fluid (CSF) biomarkers can identify individuals with Alzheimer's disease (AD) pathology (eg, amyloid plaques, neurofibrillary tangles), but defined analyte cut-points using high-throughput automated assays are necessary for general clinical use. Methods: CSF amyloid β42 peptide (Aβ42), t-tau, and t-tau/Aβ42 were quantified by the Lumipulse platform in two test cohorts (A/B: Eisai BAN2401-201/MISSION AD E2609-301/302, n = 138; C: Knight Alzheimer's Disease Research Center (ADRC), n = 198), and receiver operating characteristic (ROC) curve analyses defined cut-points corresponding best to amyloid determinations using positron emission tomography (PET) imaging. The best-performing cut-point was then validated as a predictor of amyloid status in an independent cohort (D: MISSION AD E2609-301/302, n = 240). Results: Virtually identical t-tau/Aβ42 cut-points (∼0.54) performed best in both test cohorts and with similar accuracy (areas under ROC curve [AUCs] [A/B: 0.95; C: 0.94]). The cut-point yielded an overall percent agreement with amyloid PET of 85.0% in validation cohort D. Discussion: Lumipulse CSF biomarker measures with validated cut-points have clinical utility in identifying AD pathology.",
keywords = "Alzheimer's disease, Lumipulse, amyloid PET, assay validation, biomarker, cerebrospinal fluid, cut-point, t-tau/Aβ42 ratio",
author = "June Kaplow and Manu Vandijck and Julia Gray and Michio Kanekiyo and Els Huyck and Traynham, {C. J.} and Rianne Esquivel and Fagan, {Anne M.} and Johan Luthman",
note = "Funding Information: informationThis study was supported by a research grant to AMF from Fujirebio and grants from the NIH National Institute on Aging (P01AG026276, P01AG03991, and P50AG05681). Additional support for imaging was provided by the Barnes Jewish Hospital Foundation and NIH P30NS098577, R01EB009352, and UL1TR000448. The clinical trials and associated analyses were funded by Eisai Inc.The authors would like to express their gratitude to the clinical trial participants and research volunteers who participated in the studies from which these data were obtained and their supportive families. The authors would also like to thank the Clinical, Biomarker, Genetics, and Imaging Cores at the Knight Alzheimer's Disease Research Center at Washington University in St. Louis for sample and data collection and the international project team leaders for MISSION AD and BAN2401 trial support, Drs. Bruce Albala and Veronika Logovinsky and their respective study directors Drs. Michelle Gee, Luigi Giorgi, and Chad Swanson. We would also like to acknowledge the helpful discussions with Drs. Roger Moonen, Bart DeDecker, Nathalie LeBastard (Fujirebio Europe), and John Lawson (Fujirebio Diagnostics, Inc.). A.M.F. is supported by NIH grants including P01AG026276, P01AG03991, and P50AG0568, and has received past research funding from Roche Diagnostics and Fujirebio. She is on the scientific advisory boards of AbbVie, Genentech, and Roche Diagnostics and consults for Araclon/Grifols, Biogen, and Diadem SLR. J.G. has no reported conflicts. M.V. and E.H. are employees of Fujirebio-Europe. C.T. and R.E. are employees of Fujirebio Diagnostics, Inc. J.K. and M.K. are employees of Eisai, Inc. J.L. is a full-time employee of H. Lundbeck A/D, Copenhagen, DK, and eligible to receive stock options in Lundbeck. At the time of the work conducted in this study, J.L. was a full-time employee of Eisai, Inc. J.L. owns shares in Merck Co, Inc. and AstraZeneca AB. Funding Information: The authors would like to express their gratitude to the clinical trial participants and research volunteers who participated in the studies from which these data were obtained and their supportive families. The authors would also like to thank the Clinical, Biomarker, Genetics, and Imaging Cores at the Knight Alzheimer's Disease Research Center at Washington University in St. Louis for sample and data collection and the international project team leaders for MISSION AD and BAN2401 trial support, Drs. Bruce Albala and Veronika Logovinsky and their respective study directors Drs. Michelle Gee, Luigi Giorgi, and Chad Swanson. We would also like to acknowledge the helpful discussions with Drs. Roger Moonen, Bart DeDecker, Nathalie LeBastard (Fujirebio Europe), and John Lawson (Fujirebio Diagnostics, Inc.). A.M.F. is supported by NIH grants including P01AG026276, P01AG03991, and P50AG0568, and has received past research funding from Roche Diagnostics and Fujirebio. She is on the scientific advisory boards of AbbVie, Genentech, and Roche Diagnostics and consults for Araclon/Grifols, Biogen, and Diadem SLR. J.G. has no reported conflicts. M.V. and E.H. are employees of Fujirebio‐Europe. C.T. and R.E. are employees of Fujirebio Diagnostics, Inc. J.K. and M.K. are employees of Eisai, Inc. J.L. is a full‐time employee of H. Lundbeck A/D, Copenhagen, DK, and eligible to receive stock options in Lundbeck. At the time of the work conducted in this study, J.L. was a full‐time employee of Eisai, Inc. J.L. owns shares in Merck Co, Inc. and AstraZeneca AB. Publisher Copyright: {\textcopyright} 2020 the Alzheimer's Association",
year = "2020",
month = jan,
day = "1",
doi = "10.1002/alz.12000",
language = "English",
volume = "16",
pages = "144--152",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
number = "1",
}