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Scientific article
Open access
English

Specific detection of tau seeding activity in Alzheimer's disease using rationally designed biosensor cells

Published inMolecular neurodegeneration, vol. 18, no. 1, 53
Publication date2023-08-08
First online date2023-08-08
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.

eng
Keywords
  • Alzheimer’s disease
  • Biosensor cells
  • Prion-like propagation
  • Seeding
  • Tau
  • Humans
  • Alzheimer Disease / metabolism
  • Tauopathies / metabolism
  • tau Proteins / metabolism
  • Brain / metabolism
  • Biosensing Techniques
Funding
Citation (ISO format)
LATHUILIÈRE, Aurélien et al. Specific detection of tau seeding activity in Alzheimer’s disease using rationally designed biosensor cells. In: Molecular neurodegeneration, 2023, vol. 18, n° 1, p. 53. doi: 10.1186/s13024-023-00643-2
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Identifiers
ISSN of the journal1750-1326
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