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

Wade Self, Washington University School of Medicine in St. Louis
Khader Awwad, Abbvie Germany GmbH Co KG
John Paul Savaryn, Abbvie Inc
Michael Schulz, Abbvie Germany GmbH Co KG


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.