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Abstract #106450 Published in IGR 23-3
CSF tau microtubule-binding region identifies pathological changes in primary tauopathies
Horie K; Barthélemy NR; Spina S; VandeVrede L; He Y; Paterson RW; Wright BA; Day GS; Davis AA; Karch CM; Seeley WW; Perrin RJ; Koppisetti RK; Shaikh F; Lago AL; Heuer HW; Ghoshal N; Gabelle A; Miller BL; Boxer AL; Bateman RJ; Sato CNature Medicine 2022; 28: 2547-2554
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 and MTBR-tau) 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 and MTBR-tau may represent the first affirmative biomarkers to aid in the diagnosis of primary tauopathies and facilitate clinical trial designs.
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