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Sensitive Detection of Proteopathic Seeding Activity with FRET Flow Cytometry
Published on: December 8, 2015
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Widespread tau seeding activity at early Braak stages
Jennifer L Furman1, Jaime Vaquer-Alicea1, Charles L White2
1Center for Alzheimer's and Neurodegenerative Diseases, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Acta Neuropathologica
|November 24, 2016
Summary
Early tau seeding activity, detected before phospho-tau accumulation, suggests transcellular propagation drives Alzheimer's disease (AD) pathology. This finding may aid in early diagnosis and understanding disease progression.
Area of Science:
- Neuroscience
- Biochemistry
- Pathology
Background:
- Transcellular propagation of tau aggregates is implicated in Alzheimer's disease (AD) and tauopathy progression.
- Braak staging categorizes neurodegeneration based on phospho-tau accumulation in specific brain regions.
- Previous research developed a sensitive flow cytometry assay for quantifying tau seeding activity using FRET.
Purpose of the Study:
- To investigate whether tau seeding activity precedes phospho-tau accumulation in human AD brains.
- To measure tau seeding activity across multiple brain regions in relation to Braak stage and cognitive decline.
Main Methods:
- Utilized a FRET-based flow cytometry assay to quantify tau seeding activity.
- Analyzed 104 fresh-frozen human AD brain samples across all Braak stages.
- Examined seeding activity in different brain regions and detergent-insoluble fractions.
Main Results:
- Widespread tau seeding activity was detected, even in regions without detectable phospho-tau.
- Seeding activity was found in insoluble fractions where tau was not detectable by ELISA.
- Seeding activity positively correlated with Braak stage and negatively with Mini-Mental State Examination (MMSE) scores.
Conclusions:
- Results support the hypothesis of early transcellular propagation of tau seeds preceding neuropathological changes in AD.
- The FRET-based seeding assay shows potential for early detection and complements existing tauopathy classification methods.
