학술논문
An immuno-enrichment free, validated quantification of tau protein in human CSF by LC-MS/MS.
Document Type
Article
Source
Subject
*TAU proteins
*MONOCLONAL antibodies
*LIQUID chromatography-mass spectrometry
*ALZHEIMER'S disease
*CEREBROSPINAL fluid
*CEREBROSPINAL fluid examination
*NEURODEGENERATION
*DRUG development
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Language
ISSN
1932-6203
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. [ABSTRACT FROM AUTHOR]