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CSF tau microtubule-binding region identifies pathological changes in primary tauopathies
Kanta Horie1,2, Nicolas R Barthélemy1,2, Salvatore Spina3
1Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
Nature Medicine
|November 24, 2022
Summary
New cerebrospinal fluid (CSF) biomarkers targeting 4 repeat tau (4R-tau) show promise for diagnosing primary tauopathies like corticobasal degeneration (CBD). These MTBR-tau measures could aid in clinical trials for neurodegenerative diseases.
Area of Science:
- Neuroscience
- Biochemistry
- Biomarker Discovery
Background:
- Current Alzheimer's disease (AD) research lacks fluid biomarkers for other tauopathies.
- Diagnosis and theragnosis for tauopathies beyond AD remain challenging.
Purpose of the Study:
- To identify and validate novel fluid biomarkers for primary tauopathies.
- To investigate the diagnostic utility of specific 4-repeat tau (4R-tau) species in cerebrospinal fluid (CSF).
Main Methods:
- Immunoprecipitation and mass spectrometry were used to analyze tau species.
- Quantification of microtubule-binding region tau (MTBR-tau) isoforms (MTBR-tau275 and MTBR-tau282) in brain and CSF samples.
- Statistical analysis, including receiver operating characteristic (ROC) curves, to assess diagnostic accuracy.
Main Results:
- Brain levels of MTBR-tau isoforms increased in corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), frontotemporal lobar degeneration with MAPT mutations (FTLD-MAPT), and AD.
- CSF levels of MTBR-tau isoforms showed an inverse correlation, decreasing in CBD, FTLD-MAPT, and AD compared to controls.
- CSF MTBR-tau measures demonstrated high reproducibility and diagnostic accuracy in distinguishing CBD from controls (AUC=0.889) and PSP (AUC=0.886).
Conclusions:
- CSF MTBR-tau275 and MTBR-tau282 represent potential first-in-class fluid biomarkers for primary tauopathies.
- These biomarkers may significantly aid in the diagnosis of tauopathies and improve clinical trial design.
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