Abstract
Abstract
Background
The prion-like propagation of tau in neurodegenerative disorders implies that misfolded pathological tau can recruit the normal protein and template its aggregation. Here, we report the methods for the development of sensitive biosensor cell lines for the detection of tau seeding activity.
Results
We performed the rational design of novel tau probes based on the current structural knowledge of pathological tau aggregates in Alzheimer’s disease. We generated Förster resonance energy transfer (FRET)-based biosensor stable cell lines and characterized their sensitivity, specificity, and overall ability to detect bioactive tau in human samples. As compared to the reference biosensor line, the optimized probe design resulted in an increased efficiency in the detection of tau seeding. The increased sensitivity allowed for the detection of lower amount of tau seeding competency in human brain samples, while preserving specificity for tau seeds found in Alzheimer’s disease.
Conclusions
This next generation of FRET-based biosensor cells is a novel tool to study tau seeding activity in Alzheimer’s disease human samples, especially in samples with low levels of seeding activity, which may help studying early tau-related pathological events.
Funder
AbbVie
Rainwater Charitable Foundation
National Institute of Health
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
Alzheimer's Association
Stiftung Professor Dr. Max Cloëtta
H2020 Marie Skłodowska-Curie Actions
Publisher
Springer Science and Business Media LLC
Subject
Cellular and Molecular Neuroscience,Neurology (clinical),Molecular Biology
Cited by
3 articles.
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