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

Research output: Contribution to journalArticlepeer-review

633 Scopus citations


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
Issue number6
StatePublished - Jun 18 2014

ASJC Scopus subject areas

  • Neuroscience(all)


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