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 and Diamond, Marc I (2014) Distinct tau prion strains propagate in cells and mice and define different tauopathies. Neuron, 82 (6). pp. 1271-1288. ISSN 0896-6273

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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”) in vivo that link structure to patterns 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 in vitro that induce distinct pathologies in vivo 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.

Item Type: Article
Schools and Departments: School of Life Sciences > Biochemistry
Subjects: Q Science
Depositing User: Julian Thorpe
Date Deposited: 02 Jun 2014 08:45
Last Modified: 07 Mar 2017 08:18
URI: http://sro.sussex.ac.uk/id/eprint/48849

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