Staging primary tauopathies with tau proteoforms

Project summary Recent development in biomarker assays measuring amyloid beta and tau for Alzheimer’s disease (AD) and an accelerated approval of anti-amyloid antibody, Lecanemab, defined a new era of AD research. 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), making clinical trial designs challenging. We have recently identified specific forms of tau protein in cerebrospinal fluid (CSF) that reflect brain tau pathology and can identify subsets of primary tauopathies from healthy control groups and other tauopathies. In this study, we propose to define when and which tau proteoforms change during disease progression in familial and sporadic primary tauopathies. If successful, this study will facilitate accurate diagnosis of primary tauopathies, determining clinical trial eligibility, evaluating drug efficacies, and developing treatment based on underlying neuropathology in primary tauopathies. If successful, this study will start to realize personal medicine for primary tauopathies and bridge the knowledge gap between AD research.