title: Distinct tau prion strains propagate in cells and mice and define different tauopathies.
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.
authors.affiliation: Department of Neurology, Washington University in St. Louis, St. Louis, MO 63105, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Sanders
authors.affiliation: Department of Neurology, Washington University in St. Louis, St. Louis, MO 63105, USA.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Kaufman
authors.affiliation: Department of Neurology, Washington University in St. Louis, St. Louis, MO 63105, USA.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: DeVos
authors.affiliation: Department of Neurology, Washington University in St. Louis, St. Louis, MO 63105, USA.
authors.forename: Apurwa M
authors.initials: AM
authors.lastname: Sharma
authors.affiliation: Department of Neurology, Washington University in St. Louis, St. Louis, MO 63105, USA.
authors.forename: Hilda
authors.initials: H
authors.lastname: Mirbaha
authors.affiliation: Department of Neurology, Washington University in St. Louis, St. Louis, MO 63105, USA.
authors.forename: Aimin
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Neurology, Washington University in St. Louis, St. Louis, MO 63105, USA.
authors.forename: Scarlett J
authors.initials: SJ
authors.lastname: Barker
authors.affiliation: School of Life Sciences, University of Sussex, Falmer BN1 9QG, UK.
authors.forename: Alex C
authors.initials: AC
authors.lastname: Foley
authors.affiliation: School of Life Sciences, University of Sussex, Falmer BN1 9QG, UK.
authors.forename: Julian R
authors.initials: JR
authors.lastname: Thorpe
authors.affiliation: School of Life Sciences, University of Sussex, Falmer BN1 9QG, UK.
authors.forename: Louise C
authors.initials: LC
authors.lastname: Serpell
authors.affiliation: Department of Neurology, Washington University in St. Louis, St. Louis, MO 63105, USA.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Miller
authors.affiliation: Department of Neurology and Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Lea T
authors.initials: LT
authors.lastname: Grinberg
authors.affiliation: Department of Neurology and Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: William W
authors.initials: WW
authors.lastname: Seeley
authors.affiliation: Department of Neurology, Washington University in St. Louis, St. Louis, MO 63105, USA. Electronic address: diamondm@neuro.wustl.edu.
authors.forename: Marc I
authors.initials: MI
authors.lastname: Diamond
mesh_terms: D000818:Animals; D018450:Disease Progression; D057809:HEK293 Cells; D006624:Hippocampus / Q000473:pathology* / Q000502:physiology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D019636:Neurodegenerative Diseases / Q000473:pathology*; D058225:Plaque, Amyloid / Q000473:pathology; D011328:Prions / Q000502:physiology*; D024801:Tauopathies / Q000235:genetics / Q000473:pathology*; D016875:tau Proteins / Q000502:physiology*
chemical_list: D011328:Prions; D016875:tau Proteins