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

Kanta HorieNicolas R BarthélemySalvatore SpinaLawren VandeVredeYingxin HeRoss W PatersonBrenton A WrightGregory S DayAlbert A DavisCeleste M KarchWilliam W SeeleyRichard J PerrinRama K KoppisettiFaris ShaikhArgentina Lario LagoHilary W HeuerNupur GhoshalAudrey GabelleBruce L MillerAdam L BoxerRandell J BatemanChihiro Sato
Published in: Nature medicine (2022)
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-tau 275 and MTBR-tau 282 ) 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-tau 275 and MTBR-tau 282 may represent the first affirmative biomarkers to aid in the diagnosis of primary tauopathies and facilitate clinical trial designs.
Keyphrases
  • cerebrospinal fluid
  • clinical trial
  • mass spectrometry
  • multiple sclerosis
  • randomized controlled trial
  • minimally invasive
  • genome wide
  • ms ms
  • study protocol
  • double blind