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Distinct tau prion strains propagate in cells and mice and define different tauopathies
journal contribution
posted on 2023-06-08, 17:27 authored by 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 SerpellLouise Serpell, Timothy M Miller, Lea T Grinberg, William W Seeley, Marc I DiamondPrion-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.
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Publication status
- Published
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- Published version
Journal
NeuronISSN
0896-6273Publisher
ElsevierExternal DOI
Issue
6Volume
82Page range
1271-1288Department affiliated with
- Biochemistry Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2014-06-02First Open Access (FOA) Date
2016-02-05First Compliant Deposit (FCD) Date
2016-02-05Usage metrics
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