Distinct tau prion strains propagate in cells and mice and define different tauopathies

David W. Sanders, Sarah K. Kaufman, Sarah L. DeVos, Apurwa M. Sharma, Hilda Mirbaha, Aimin Li, Scarlett J. Barker, Alex C. Foley, Julian R. Thorpe, Louise C. Serpell, Timothy M. Miller, Lea T. Grinberg, William W. Seeley, Marc I. Diamond

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Abstract

Prion-like propagation of tau aggregation might underlie the stereotyped progression of neurodegenerative tauopathies. True prions stably maintain unique conformations ("strains") invivo that link structure topatterns 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 invitro that induce distinct pathologies invivo 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.

Original languageEnglish (US)
Pages (from-to)1271-1288
Number of pages18
JournalNeuron
Volume82
Issue number6
DOIs
StatePublished - Jun 18 2014

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Tauopathies
Prions
Pathology
Amyloid
Transgenic Mice
Clone Cells
Therapeutics

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Sanders, D. W., Kaufman, S. K., DeVos, S. L., Sharma, A. M., Mirbaha, H., Li, A., ... Diamond, M. I. (2014). Distinct tau prion strains propagate in cells and mice and define different tauopathies. Neuron, 82(6), 1271-1288. https://doi.org/10.1016/j.neuron.2014.04.047

Distinct tau prion strains propagate in cells and mice and define different tauopathies. / Sanders, David W.; Kaufman, Sarah K.; DeVos, Sarah L.; Sharma, Apurwa M.; Mirbaha, Hilda; Li, Aimin; Barker, Scarlett J.; Foley, Alex C.; Thorpe, Julian R.; Serpell, Louise C.; Miller, Timothy M.; Grinberg, Lea T.; Seeley, William W.; Diamond, Marc I.

In: Neuron, Vol. 82, No. 6, 18.06.2014, p. 1271-1288.

Research output: Contribution to journalArticle

Sanders, DW, Kaufman, SK, DeVos, SL, Sharma, AM, Mirbaha, H, Li, A, Barker, SJ, Foley, AC, Thorpe, JR, Serpell, LC, Miller, TM, Grinberg, LT, Seeley, WW & Diamond, MI 2014, 'Distinct tau prion strains propagate in cells and mice and define different tauopathies', Neuron, vol. 82, no. 6, pp. 1271-1288. https://doi.org/10.1016/j.neuron.2014.04.047
Sanders DW, Kaufman SK, DeVos SL, Sharma AM, Mirbaha H, Li A et al. Distinct tau prion strains propagate in cells and mice and define different tauopathies. Neuron. 2014 Jun 18;82(6):1271-1288. https://doi.org/10.1016/j.neuron.2014.04.047
Sanders, David W. ; Kaufman, Sarah K. ; DeVos, Sarah L. ; Sharma, Apurwa M. ; Mirbaha, Hilda ; Li, Aimin ; Barker, Scarlett J. ; Foley, Alex C. ; Thorpe, Julian R. ; Serpell, Louise C. ; Miller, Timothy M. ; Grinberg, Lea T. ; Seeley, William W. ; Diamond, Marc I. / Distinct tau prion strains propagate in cells and mice and define different tauopathies. In: Neuron. 2014 ; Vol. 82, No. 6. pp. 1271-1288.
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