An immuno-enrichment free, validated quantification of tau protein in human CSF by LC-MS/MS

Wade Self; Khader Awwad; John Paul Savaryn; Michael Schulz

doi:10.1371/journal.pone.0269157

An immuno-enrichment free, validated quantification of tau protein in human CSF by LC-MS/MS

Wade Self, Khader Awwad, John Paul Savaryn, Michael Schulz

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Tau protein is a key target of interest in developing therapeutics for neurodegenerative diseases. Here, we sought to develop a method that quantifies extracellular tau protein concentrations in human cerebrospinal fluid (CSF) without antibody-based enrichment strategies. We demonstrate that the fit-for-purpose validated method in Alzheimer’s Disease CSF is limited to quasi quantitative measures of tau surrogate peptides. We also provide evidence that CSF total Tau measures by LC-MS are feasible in the presence of monoclonal therapeutic antibodies in human CSF. Our Tau LC-MS/MS method is a translational bioanalytical tool for assaying target engagement and pharmacodynamics for anti-tau antibody drug development campaigns.

Original language	English
Article number	e0269157
Journal	PloS one
Volume	17
Issue number	6 June
DOIs	https://doi.org/10.1371/journal.pone.0269157
State	Published - Jun 2022

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abstract = "Tau protein is a key target of interest in developing therapeutics for neurodegenerative diseases. Here, we sought to develop a method that quantifies extracellular tau protein concentrations in human cerebrospinal fluid (CSF) without antibody-based enrichment strategies. We demonstrate that the fit-for-purpose validated method in Alzheimer{\textquoteright}s Disease CSF is limited to quasi quantitative measures of tau surrogate peptides. We also provide evidence that CSF total Tau measures by LC-MS are feasible in the presence of monoclonal therapeutic antibodies in human CSF. Our Tau LC-MS/MS method is a translational bioanalytical tool for assaying target engagement and pharmacodynamics for anti-tau antibody drug development campaigns.",

author = "Wade Self and Khader Awwad and Savaryn, {John Paul} and Michael Schulz",

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AU - Schulz, Michael

N1 - Publisher Copyright: © 2022 Self et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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AB - Tau protein is a key target of interest in developing therapeutics for neurodegenerative diseases. Here, we sought to develop a method that quantifies extracellular tau protein concentrations in human cerebrospinal fluid (CSF) without antibody-based enrichment strategies. We demonstrate that the fit-for-purpose validated method in Alzheimer’s Disease CSF is limited to quasi quantitative measures of tau surrogate peptides. We also provide evidence that CSF total Tau measures by LC-MS are feasible in the presence of monoclonal therapeutic antibodies in human CSF. Our Tau LC-MS/MS method is a translational bioanalytical tool for assaying target engagement and pharmacodynamics for anti-tau antibody drug development campaigns.

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An immuno-enrichment free, validated quantification of tau protein in human CSF by LC-MS/MS

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