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

Sarah K. Kaufman, David W. Sanders, Talitha L. Thomas, Allison J. Ruchinskas, Jaime Vaquer-Alicea, Apurwa M. Sharma, Timothy M. Miller, Marc I. Diamond

Research output: Contribution to journalArticlepeer-review

153 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)796-812
Number of pages17
JournalNeuron
Volume92
Issue number4
DOIs
StatePublished - Nov 23 2016

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

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