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Neuron. 2016 Nov 23;92(4):796-812. doi: 10.1016/j.neuron.2016.09.055. Epub 2016 Oct 27.

Tau Prion Strains Dictate Patterns of Cell Pathology, Progression Rate, and Regional Vulnerability In Vivo.

Author information

1
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.
2
Center for Alzheimer's and Neurodegenerative Diseases, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA0, USA.
3
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.
4
Department of Neurology, Washington University in St. Louis, St. Louis, MO 63130, USA.
5
Center for Alzheimer's and Neurodegenerative Diseases, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA0, USA. Electronic address: marc.diamond@utsouthwestern.edu.

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.

KEYWORDS:

cell model; prion; prion-like; seeding activity; strain; tau; tau pathology; tauopathy; transcellular propagation

Comment in

PMID:
27974162
PMCID:
PMC5392364
DOI:
10.1016/j.neuron.2016.09.055
[Indexed for MEDLINE]
Free PMC Article

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