This study investigates the role of brain-derived tau (BD-tau) in blood as a biomarker for Alzheimer's disease (AD). The researchers used blood-based BD-tau to profile participants across four independent cohorts, examining its association with cognitive decline and atrophy rates. They found that blood-based BD-tau levels increased with the presence of amyloid-beta (Aβ) pathology and neurodegeneration, as determined by cerebrospinal fluid (CSF) biomarkers. Individuals with blood-based p-tau+/BD-tau+ profiles showed faster cognitive decline and atrophy rates, regardless of their baseline cognitive status. BD-tau showed weaker correlations with age, renal function, comorbidities, and race/ethnicity compared to other blood biomarkers. The study demonstrates that blood-based BD-tau is a valuable biomarker for identifying AD patients at risk of short-term cognitive decline and atrophy, with implications for clinical trials and the implementation of anti-Aβ therapies.This study investigates the role of brain-derived tau (BD-tau) in blood as a biomarker for Alzheimer's disease (AD). The researchers used blood-based BD-tau to profile participants across four independent cohorts, examining its association with cognitive decline and atrophy rates. They found that blood-based BD-tau levels increased with the presence of amyloid-beta (Aβ) pathology and neurodegeneration, as determined by cerebrospinal fluid (CSF) biomarkers. Individuals with blood-based p-tau+/BD-tau+ profiles showed faster cognitive decline and atrophy rates, regardless of their baseline cognitive status. BD-tau showed weaker correlations with age, renal function, comorbidities, and race/ethnicity compared to other blood biomarkers. The study demonstrates that blood-based BD-tau is a valuable biomarker for identifying AD patients at risk of short-term cognitive decline and atrophy, with implications for clinical trials and the implementation of anti-Aβ therapies.