@article{a283691235e3449288e7f9cf603443d7,
title = "Performance of plasma phosphorylated tau 181 and 217 in the community",
abstract = "Plasma phosphorylated tau 181 (P-tau181) and 217 (P-tau217) are indicators of both amyloid and tau pathology in clinical settings, but their performance in heterogeneous community-based populations is unclear. We examined P-tau181 and P-tau217 (n = 1,329, aged 30–98 years), in the population-based Mayo Clinic Study of Aging. Continuous, unadjusted plasma P-tau181 and P-tau217 predicted abnormal amyloid positron-emission tomography (PET) (area under the receiver operating characteristic curve (AUROC) = 0.81–0.86) and tau PET entorhinal cortex (AUROC > 0.80), but was less predictive of a tau PET temporal region of interest (AUROC < 0.70). Multiple comorbidities were associated with higher plasma P-tau181 and P-tau217 levels; the difference between participants with and without chronic kidney disease (CKD) was similar to the difference between participants with and without elevated brain amyloid. The exclusion of participants with CKD and other comorbidities affected the establishment of a normal reference range and cutpoints. Understanding the effect of comorbidities on P-tau181 and P-tau217 levels is important for their future interpretation in the context of clinical screening, diagnosis or prognosis at the population level.",
author = "Mielke, {Michelle M.} and Dage, {Jeffrey L.} and Frank, {Ryan D.} and Alicia Algeciras-Schimnich and Knopman, {David S.} and Lowe, {Val J.} and Guojun Bu and Prashanthi Vemuri and Jonathan Graff-Radford and Jack, {Clifford R.} and Petersen, {Ronald C.}",
note = "Funding Information: Funding for this study was provided by grants from the National Institutes of Health (NIH) (U01 AG006786 to M.M.M., C.R.J. and R.C.P.; R37 AG011378 to C.R.J.; R01 NS097495 to P.V.; P30 AG062677 to R.C.P.; RF1 AG069052 to M.M.M., J.G-R. and P.V.; and R01 AG041851 to C.R.J. and D.S.K.) and the GHR Foundation (to R.C.P.). This study was made possible using the resources of the REP, which is supported by the NIH National Institute on Aging under award no. R01 AG034676. Meso Scale Discovery P-tau181 and P-tau217 assays were performed at Eli Lilly and Company. The funders of the study had no role in study design, data collection, data analysis, data interpretation or writing of the report. The corresponding author had full access to all data in the study, and all authors had final responsibility for the decision to submit for publication. Funding Information: M.M.M. has served as a consultant for Biogen, Brain Protection Company and Labcorp. J.L.D. was previously an employee and is still a minor shareholder of Eli Lilly and Company. J.L.D. is an inventor on patents or patent applications of Eli Lilly and Company relating to the assays, methods, reagents and/or compositions of matter used in this work. J.L.D. has also served as a consultant for Karuna Therapeutics and received research support from ADx Neurosciences, Roche Diagnostics and Eli Lilly and Company. R.D.F. and A.A.-S. report no conflicts. D.S.K. serves on a data safety monitoring board for the Dominantly Inherited Alzheimer Network (DIAN) study. D.S.K. also serves on a data safety monitoring board for Biogen but receives no personal compensation. D.S.K. is an investigator in clinical trials sponsored by Biogen, Lilly Pharmaceuticals and the University of Southern California. D.S.K. serves as a consultant for Roche, Samus Therapeutics, Third Rock and Alzeca Biosciences but receives no personal compensation. V.J.L. received consulting fees from Bayer Schering Pharma, Piramal Life Sciences and Merck Research, and grants from GE Healthcare, Siemens Molecular Imaging, Avid Radiopharmaceuticals and the NIH. G.B. serves as a consultant for AbbVie, E-Scape and SciNeuro. P.V. received speaking fees from Miller Medical Communications. J.G.-R. receives NIH funding and serves as an assistant editor for Neurology. C.R.J. serves on an independent data monitoring board for Roche, has served as a speaker for Eisai and consulted for Biogen but receives no personal compensation from any commercial entity. C.R.J. receives research support from the NIH and the Alexander Family Alzheimer{\textquoteright}s Disease Research Professorship of Mayo Clinic. R.C.P. received consulting fees from Hoffman-La Roche, Merck, Genentech, Biogen, GE Healthcare and Eisai. Funding Information: Funding for this study was provided by grants from the National Institutes of Health (NIH) (U01 AG006786 to M.M.M., C.R.J. and R.C.P.; R37 AG011378 to C.R.J.; R01 NS097495 to P.V.; P30 AG062677 to R.C.P.; RF1 AG069052 to M.M.M., J.G-R. and P.V.; and R01 AG041851 to C.R.J. and D.S.K.) and the GHR Foundation (to R.C.P.). This study was made possible using the resources of the REP, which is supported by the NIH National Institute on Aging under award no. R01 AG034676. Meso Scale Discovery P-tau181 and P-tau217 assays were performed at Eli Lilly and Company. The funders of the study had no role in study design, data collection, data analysis, data interpretation or writing of the report. The corresponding author had full access to all data in the study, and all authors had final responsibility for the decision to submit for publication. Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2022",
month = jul,
doi = "10.1038/s41591-022-01822-2",
language = "English (US)",
volume = "28",
pages = "1398--1405",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "7",
}