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

© 2022. The Author(s)..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:28

Enthalten in:

Nature medicine - 28(2022), 12 vom: 24. Dez., Seite 2547-2554

Sprache:

Englisch

Beteiligte Personen:

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

Links:

Volltext

Themen:

Biomarkers
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Tau Proteins

Anmerkungen:

Date Completed 02.01.2023

Date Revised 28.02.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1038/s41591-022-02075-9

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM349375224