Tau seeding activity in the cerebrospinal fluid of Alzheimer disease patients predicts short-term cognitive decline.

BACKGROUND: Alzheimer disease (AD) clinical progression is highly heterogeneous, making its prediction essential for the development of effective therapies. The advancement of cognitive decline in AD is tightly linked to the spread of pathological tau protein aggregates in the brain, through tau seeding properties. METHODS: We developed a cellular biosensor to measure tau seeding activity from cerebrospinal fluid (CSF) and human brain lysates. Longitudinal analysis of cognitive function was correlated with biosensor response. RESULTS: Individuals with CSF exhibiting high or intermediate seeding activity experienced more rapid cognitive decline compared to those with low seeding. High tau seeding was associated with total and phosphorylated tau biomarkers in AD. The biosensor also predicts the potential of human AD brain lysates to induce tau aggregation upon experimental transmission in animal models. CONCLUSIONS: These results suggest that seeding activity might be a relevant biomarker to forecast AD pathogenicity and clinical progression.