Project summary Over the past several years, blood-based biomarkers that accurately detect Alzheimer’s Disease (AD) brain pathology have been developed. However, there are no specific fluid or imaging biomarkers for primary tauopathies including progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and frontotemporal lobar degeneration (FTLD). We have recently identified specific species of tau in cerebrospinal fluid (CSF) that can identify subsets of primary tauopathies from healthy control groups and other tauopathies with moderate specificity and sensitivity. In this study, we propose to optimize mass spectrometry methods to better distinguish primary tauopathies in CSF. Based on the new methods, we will translate these primary tauopathy biomarkers to blood and test if they correlate with the biomarker measures in paired CSF. This study will provide first measures of primary tauopathies in blood and prepare for large cohort studies looking into primary tauopathy CSF and blood to distinguish subgroups of primary tauopathies or tauopathies from other neurological or psychiatric diseases. If blood biomarkers are developed, it will likely be widely used and could facilitate primary tauopathy research and diagnoses.