title: Tau Prion Strains Dictate Patterns of Cell Pathology, Progression Rate, and Regional Vulnerability In Vivo.
abstract: Tauopathies are neurodegenerative disorders that affect distinct brain regions, progress at different rates, and exhibit specific patterns of tau accumulation. The source of this diversity is unknown. We previously characterized two tau strains that stably maintain unique conformations in vitro and in vivo, but did not determine the relationship of each strain to parameters that discriminate between tauopathies such as regional vulnerability or rate of spread. We have now isolated and characterized 18 tau strains in cells based on detailed biochemical and biological criteria. Inoculation of PS19 transgenic tau (P301S) mice with these strains causes strain-specific intracellular pathology in distinct cell types and brain regions, and induces different rates of network propagation. In this system, strains alone are sufficient to account for diverse neuropathological presentations, similar to those that define human tauopathies. Further study of these strains can thus establish a structural logic that governs these biological effects.
authors.affiliation: Program in Neuroscience, Washington University in St. Louis, St. Louis, MO 63130, USA; Center for Alzheimer's and Neurodegenerative Diseases, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA0, USA.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Kaufman
authors.affiliation: Program in Neuroscience, Washington University in St. Louis, St. Louis, MO 63130, USA; Center for Alzheimer's and Neurodegenerative Diseases, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA0, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Sanders
authors.affiliation: Center for Alzheimer's and Neurodegenerative Diseases, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA0, USA.
authors.forename: Talitha L
authors.initials: TL
authors.lastname: Thomas
authors.affiliation: Center for Alzheimer's and Neurodegenerative Diseases, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA0, USA.
authors.forename: Allison J
authors.initials: AJ
authors.lastname: Ruchinskas
authors.affiliation: Center for Alzheimer's and Neurodegenerative Diseases, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA0, USA.
authors.forename: Jaime
authors.initials: J
authors.lastname: Vaquer-Alicea
authors.affiliation: Center for Alzheimer's and Neurodegenerative Diseases, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA0, USA; Program in Biochemistry, Washington University in St. Louis, St. Louis, MO 63130, USA.
authors.forename: Apurwa M
authors.initials: AM
authors.lastname: Sharma
authors.affiliation: Department of Neurology, Washington University in St. Louis, St. Louis, MO 63130, USA.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Miller
authors.affiliation: Center for Alzheimer's and Neurodegenerative Diseases, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA0, USA. Electronic address: marc.diamond@utsouthwestern.edu.
authors.forename: Marc I
authors.initials: MI
authors.lastname: Diamond
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D000072002:Prion Proteins / Q000378:metabolism*; D024801:Tauopathies / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000072002:Prion Proteins; D016875:tau Proteins
keywords: cell model; prion; prion-like; seeding activity; strain; tau; tau pathology; tauopathy; transcellular propagation