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.

尽管最近在阿尔茨海默病 (AD) 的液体生物标志物研究方面取得了进展，但还没有液体生物标志物或成像示踪剂可用于其他 tau 病的诊断和/或治疗。使用免疫沉淀和质谱法，我们显示来自微管结合区（MTBR-tau ₂₇₅和 MTBR-tau ₂₈₂）的 4 重复（4R）同种型特异性 tau 种类在大脑皮质基底变性（CBD）、进行性核上性麻痹（ PSP)、额颞叶变性 (FTLD)-MAPT和AD 但在 CBD、FTLD- MAPT的脑脊液 (CSF) 中呈负相关和 AD 相比，控制和其他 FTLD-tau（例如，匹克氏病）。CSF MTBR-tau 测量在反复腰椎穿刺中可重现，可用于区分 CBD 与控制（曲线下的接收器操作特征区域（AUC）= 0.889）和其他 FTLD-tau，例如 PSP（AUC = 0.886）。CSF MTBR-tau ₂₇₅和 MTBR-tau ₂₈₂可能代表第一个肯定的生物标志物，以帮助诊断原发性 tau 病并促进临床试验设计。