CSF tau microtubule-binding region identifies pathological changes in primary tauopathies.
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| Abstract |
Despite recent advances in fluid biomarker research in Alzheimer'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'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.
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| Authors | Kanta Horie, Nicolas R Barthélemy, Salvatore Spina, Lawren VandeVrede, Yingxin He, Ross W Paterson, Brenton A Wright, Gregory S Day, Albert A Davis, Celeste M Karch, William W Seeley, Richard J Perrin, Rama K Koppisetti, Faris Shaikh, Argentina Lario Lago, Hilary W Heuer, Nupur Ghoshal, Audrey Gabelle, Bruce L Miller, Adam L Boxer, Randall J Bateman, Chihiro Sato |
| Journal | Nature medicine (Nat Med) Vol. 28 Issue 12 Pg. 2547-2554 (12 2022) ISSN: 1546-170X [Electronic] United States |
| PMID | 36424467 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural) |
| Copyright | © 2022. The Author(s). |
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