Journal
NEURON
Volume 82, Issue 6, Pages 1271-1288Publisher
CELL PRESS
DOI: 10.1016/j.neuron.2014.04.047
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Categories
Funding
- Tau Consortium
- Muscular Dystrophy Association
- American Health Assistance Foundation
- Ruth K. Broad Foundation
- Harrington Discovery Institute
- NIH [1F31NS086251, 1R01NS071835, 1R01NS078398, P01AG019724, P50AG023501]
- Hope Center Alafi Neuroimaging Lab
- Neuroscience Blueprint Interdisciplinary Center Core award [P30NS057105]
- Neurodegenerative Disease Brain Bank at the University of California, San Francisco
- Consortium for Frontotemporal Dementia Research
- MRC [MR/K022105/1] Funding Source: UKRI
- Medical Research Council [MR/K022105/1] Funding Source: researchfish
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Prion-like propagation of tau aggregation might underlie the stereotyped progression of neurodegenerative tauopathies. True prions stably maintain unique conformations (strains) in vivo that link structure to patterns of pathology. We now find that tau meets this criterion. Stably expressed tau repeat domain indefinitely propagates distinct amyloid conformations in a clonal fashion in culture. Reintroduction of tau from these lines into naive cells reestablishes identical clones. We produced two strains in vitro that induce distinct pathologies in vivo as determined by successive inoculations into three generations of transgenic mice. Immunopurified tau from these mice recreates the original strains in culture. We used the cell system to isolate tau strains from 29 patients with 5 different tauopathies, finding that different diseases are associated with different sets of strains. Tau thus demonstrates essential characteristics of a prion. This might explain the phenotypic diversity of tauopathies and could enable more effective diagnosis and therapy.
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