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

Aims: 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 human cerebrospinal fluid (CSF) without antibody-based enrichment strategies. Results: We demonstrate that the fit-for-purpose validated method in Alzheimers 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. Conclusion: Our Tau LC-MS/MS method is a translational bioanalytical tool for assaying target