Comprehensive CSF Tau Profiling Identifies Soluble Tau Pathophysiological Stages in Dominantly Inherited Alzheimer Network (DIAN): Implications for the DIAN‐TU Tau Next Generation Platform

Brain tau aggregation is a pathological hallmark of Alzheimer’s disease (AD) and the tau microtubule binding region (MTBR) is the core of AD tau tangles. Recently, we identified the enrichment of some specific MTBR species in sporadic AD brain tangles. Corresponding soluble MTBR species in the CSF increased together with clinical progression and tau pathology measured by tau‐PET. Because extracellular MTBR‐tau was discovered in human AD, MTBR‐tau has become a high priority target for antibodies binding this region. In this study, we sought to determine when these MTBR‐tau changes occurred and the relationship to clinical, cognitive and biomarker changes in the DIAN.