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


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.

SUBMITTER: Self W 

PROVIDER: S-EPMC9162344 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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

Self Wade W   Awwad Khader K   Savaryn John Paul JP   Schulz Michael M  

PloS one 20220602 6


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  ...[more]

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