CSF tau microtubule-binding region identifies pathological changes in primary tauopathies

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. BoxerRandall J. Bateman, Chihiro Sato

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


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.

Original languageEnglish
Pages (from-to)2547-2554
Number of pages8
JournalNature medicine
Issue number12
StatePublished - Dec 2022


Dive into the research topics of 'CSF tau microtubule-binding region identifies pathological changes in primary tauopathies'. Together they form a unique fingerprint.

Cite this