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Updated: Jul 8, 2026
Sensitive Detection of Proteopathic Seeding Activity with FRET Flow Cytometry
Published on: December 8, 2015
Specific detection of tau seeding activity in Alzheimer's disease using rationally designed biosensor cells
Aurelien Lathuiliere1,2,3, Youhwa Jo1, Romain Perbet1,2
1Department of Neurology, Massachusetts General Hospital/Harvard Medical School, 114 16Th Street, Charlestown, MA, 02129, USA.
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.
