Journal Article

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

Spina, Salvatore, Koppisetti, Rama K., Paterson, Ross W., Shaikh, Faris, He, Yingxin, Lago, Argentina Lario, Perrin, Richard J., Seeley, William W., Gabelle, Audrey, Bateman, Randall J., Horie, Kanta, Day, Gregory S., VandeVrede, Lawren, Wright, Brenton A., Miller, Bruce L., Ghoshal, Nupur, Karch, Celeste M., Boxer, Adam L., Barthélemy, Nicolas R., Sato, Chihiro, Davis, Albert A., Heuer, Hilary W.

2022

Overview

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. Cerebrospinal fluid measures of isoform-specific tau species from the microtubule-binding region serve as the first fluid biomarkers of primary tauopathy.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 692/53/2421 / 692/617/375/365 / Alzheimer Disease - diagnosis / Alzheimer Disease - pathology / Alzheimer's disease / Binding / Biomarkers / Biomedical and Life Sciences / Biomedicine / Cancer Research / Cerebrospinal fluid / Degeneration / Diagnosis / Frontotemporal dementia / Frontotemporal Dementia - pathology / Frontotemporal Lobar Degeneration - pathology / Humans / Immunoprecipitation / Infectious Diseases / Mass spectrometry / Mass spectroscopy / Metabolic Diseases / Microtubules / Molecular Medicine / Neurodegenerative diseases / Neurosciences / Paralysis / Progressive supranuclear palsy / Tau protein / tau Proteins / Tauopathies - pathology