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Neuron. 2014 Jun 18;82(6):1271-88. doi: 10.1016/j.neuron.2014.04.047. Epub 2014 May 22.

Distinct tau prion strains propagate in cells and mice and define different tauopathies.

Author information

1
Department of Neurology, Washington University in St. Louis, St. Louis, MO 63105, USA.
2
School of Life Sciences, University of Sussex, Falmer BN1 9QG, UK.
3
Department of Neurology and Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
4
Department of Neurology, Washington University in St. Louis, St. Louis, MO 63105, USA. Electronic address: diamondm@neuro.wustl.edu.

Abstract

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.

PMID:
24857020
PMCID:
PMC4171396
DOI:
10.1016/j.neuron.2014.04.047
[Indexed for MEDLINE]
Free PMC Article

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