@article{31f7238bf1ea4c3aa6dc1b8a74ee12c9,
title = "CSF tau microtubule-binding region identifies pathological changes in primary tauopathies",
abstract = "Despite recent advances in fluid biomarker research in Alzheimer{\textquoteright}s disease (AD), there are no fluid biomarkers or imaging tracers with utility for diagnosis and/or theragnosis available for other tauopathies. Using immunoprecipitation and mass spectrometry, we show that 4 repeat (4R) isoform-specific tau species from microtubule-binding region (MTBR-tau275 and MTBR-tau282) increase in the brains of corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), frontotemporal lobar degeneration (FTLD)-MAPT and AD but decrease inversely in the cerebrospinal fluid (CSF) of CBD, FTLD-MAPT and AD compared to control and other FTLD-tau (for example, Pick{\textquoteright}s disease). CSF MTBR-tau measures are reproducible in repeated lumbar punctures and can be used to distinguish CBD from control (receiver operating characteristic area under the curve (AUC) = 0.889) and other FTLD-tau, such as PSP (AUC = 0.886). CSF MTBR-tau275 and MTBR-tau282 may represent the first affirmative biomarkers to aid in the diagnosis of primary tauopathies and facilitate clinical trial designs.",
author = "Kanta Horie and Barth{\'e}lemy, {Nicolas R.} and Salvatore Spina and Lawren VandeVrede and Yingxin He and Paterson, {Ross W.} and Wright, {Brenton A.} and Day, {Gregory S.} and Davis, {Albert A.} and Karch, {Celeste M.} and Seeley, {William W.} and Perrin, {Richard J.} and Koppisetti, {Rama K.} and Faris Shaikh and Lago, {Argentina Lario} and Heuer, {Hilary W.} and Nupur Ghoshal and Audrey Gabelle and Miller, {Bruce L.} and Boxer, {Adam L.} and Bateman, {Randall J.} and Chihiro Sato",
note = "Funding Information: This work was supported by the Rainwater Charitable Foundation (R.J.B., C.S., A.L.B., N.G., R.W.P., C.M.K., B.L.M., L.V., S.S.), National Institutes of Health (NIH)/National Institute on Aging (NIA) K01AG062796 (C.S.) and Barnes Jewish Hospital Foundation (BJHF) pilot grant no. 3945 (C.S.). Additionally, samples analyzed in this study were obtained with support from the Tau Foundation plan Alzheimer (A.G.), BIRCWH K12 HD001459 (N.G.), NIH/NIA K23 AG064029 (G.S.D.), NIH/NIA K08 AG052648 (S.S.), NIH/National Institute of Neurological Disorders and Stroke (NINDS) K08 NS101118 (A.A.D.), NIH/NINDS R01NS065667 (R.J.B.), NIH/NINDS R01NS095773 (R.J.B.), Alzheimer Disease Research Center grant no. P30 AG066444 (C.M.K.), NIH/NINDS NS110890 (C.M.K.), Association for Frontotemporal Degeneration (R.J.B., C.S., A.L.B., N.G., R.W.P., B.L.M.), NIH/NIA U19AG063911 (A.L.B.), NIH/NIA R01AG038791 (A.L.B.), NIH/NIA R01 AG073482 (A.L.B.) and NIH/NIA U24AG057437 (A.L.B.). This work was supported by resources and effort provided by the Tracy Family Stable Isotope Labeling Quantitation Center (principal investigator: R.J.B.) established by the Tracy Family, R. Frimel and G. Werths, GHR Foundation, D. Payne and the Willman Family brought together by The Foundation for Barnes-Jewish Hospital. This work was also supported by cores, resources and effort provided by Washington University Biomedical Mass Spectrometry Research Facility (NIH/National Institute of General Medical Sciences P41 GM103422) and access to equipment made possible by the Hope Center for Neurological Disorders and the Departments of Neurology and Psychiatry at the Washington University School of Medicine. Resources and effort provided by the Translational Human Neurodegenerative Disease Research Laboratory of Washington University were supported by NIH/NIA P01 AG03991 (Healthy Aging and Senile Dementia), NIH/NIA P30 AG066444 (Alzheimer{\textquoteright}s Disease Research Center) or NIH/NIA P01 AG026276 (the Adult Children Study). The UCSF Neurodegenerative Disease Brain Bank is supported by NIH/NIA P50 AG023501 and NIH/NIA P01 AG019724, Rainwater Charitable Foundation and the Bluefield Project to Cure FTD. We thank the participants and families for their contribution to this study. We thank Y. Li for advice on the power analyses. We thank M. Li and M. Sullivan for enrolling participants for the repeat lumbar puncture study. We thank the Clinical, Biomarker and Imaging Cores at the Washington University School of Medicine for participant evaluation, samples and data collection. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s41591-022-02075-9",
language = "English",
volume = "28",
pages = "2547--2554",
journal = "Nature Medicine",
issn = "1078-8956",
number = "12",
}