biostudies-literatureSanders DWNIA NIH HHSMedical Research CouncilNINDS NIH HHSNIGMS NIH HHS1271-88https://www.ebi.ac.uk/biostudies/studies/S-EPMC4171396biostudies-literatureUnknown82(6)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.NeuronDistinct tau prion strains propagate in cells and mice and define different tauopathies.PMC41713961R01NS0783981F31NS086251P01 AG019724P30 NS057105P30NS057105MR/K022105/1P01AG019724R01 NS071835T32 GM008151F31 NS086251P50 AG023501R01 NS0783981R01NS071835F30 AG048653P50AG023501Kaufman SKBarker SJGrinberg LTSharma AMSerpell LCMirbaha HMiller TMSanders DWFoley ACDeVos SLLi ADiamond MISeeley WWThorpe JRfalseDistinct tau prion strains propagate in cells and mice and define different tauopathies.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.2014-01-01T00:00:00Z2014 Jun2024-11-08T19:39:25.424Z2019-03-27T01:36:10ZS-EPMC41713962485702010.1016/j.neuron.2014.04.047