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

Nat Med. 2022 Dec;28(12):2547-2554. doi: 10.1038/s41591-022-02075-9. Epub 2022 Nov 24.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Alzheimer Disease* / diagnosis
  • Alzheimer Disease* / pathology
  • Biomarkers
  • Frontotemporal Dementia* / pathology
  • Frontotemporal Lobar Degeneration* / pathology
  • Humans
  • Microtubules
  • Tauopathies* / pathology
  • tau Proteins


  • tau Proteins
  • Biomarkers