@article{840dfd02d73b42bba09453a66d8699f5,
title = "Distinct tau prion strains propagate in cells and mice and define different tauopathies",
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.",
author = "Sanders, {David W.} and Kaufman, {Sarah K.} and DeVos, {Sarah L.} and Sharma, {Apurwa M.} and Hilda Mirbaha and Aimin Li and Barker, {Scarlett J.} and Foley, {Alex C.} and Thorpe, {Julian R.} and Serpell, {Louise C.} and Miller, {Timothy M.} and Grinberg, {Lea T.} and Seeley, {William W.} and Diamond, {Marc I.}",
note = "Funding Information: We thank John Cirrito, Peter Davies, David Holtzman, Paul Kotzbauer, Jeffrey Milbrandt, and David Piwnica-Worms for reagents. We thank Dorrie Young for help with figures and Jan Bieschke, William Dauer, Jen Dulle, Bess Frost, Brandon Holmes, Suzanne Schindler, Kevin Stein, and Heather True for critiques. Our work was funded by the Tau Consortium, Muscular Dystrophy Association, American Health Assistance Foundation, Ruth K. Broad Foundation, Harrington Discovery Institute, and the NIH (1F31NS086251, D.W.S.; 1R01NS071835, M.I.D.; 1R01NS078398, T.M.M.). This work was supported by the Hope Center Alafi Neuroimaging Lab and a P30 Neuroscience Blueprint Interdisciplinary Center Core award to Washington University (P30NS057105). Human tissue samples were provided by the Neurodegenerative Disease Brain Bank at the University of California, San Francisco, which receives funding support from NIH grants P01AG019724 and P50AG023501, the Consortium for Frontotemporal Dementia Research, and the Tau Consortium. M.I.D. acknowledges a potential conflict of interest in that he is a coinventor of antibodies used in this study (HJ9.3 and HJ8.5) that have been licensed by C2N Diagnostics through an agreement with Washington University in St. Louis. ",
year = "2014",
month = jun,
day = "18",
doi = "10.1016/j.neuron.2014.04.047",
language = "English (US)",
volume = "82",
pages = "1271--1288",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "6",
}