[HTML][HTML] CSF tau microtubule-binding region identifies pathological changes in primary tauopathies
Nature medicine, 2022•nature.com
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 …
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 …
Abstract
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.
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