@article{bbd438eba1b64a64b9f2863a710e6d0e,
title = "Tau Prion Strains Dictate Patterns of Cell Pathology, Progression Rate, and Regional Vulnerability In Vivo",
abstract = "Tauopathies are neurodegenerative disorders that affect distinct brain regions, progress at different rates, and exhibit specific patterns of tau accumulation. The source of this diversity is unknown. We previously characterized two tau strains that stably maintain unique conformations in vitro and in vivo, but did not determine the relationship of each strain to parameters that discriminate between tauopathies such as regional vulnerability or rate of spread. We have now isolated and characterized 18 tau strains in cells based on detailed biochemical and biological criteria. Inoculation of PS19 transgenic tau (P301S) mice with these strains causes strain-specific intracellular pathology in distinct cell types and brain regions, and induces different rates of network propagation. In this system, strains alone are sufficient to account for diverse neuropathological presentations, similar to those that define human tauopathies. Further study of these strains can thus establish a structural logic that governs these biological effects.",
keywords = "cell model, prion, prion-like, seeding activity, strain, tau, tau pathology, tauopathy, transcellular propagation",
author = "Kaufman, {Sarah K.} and Sanders, {David W.} and Thomas, {Talitha L.} and Ruchinskas, {Allison J.} and Jaime Vaquer-Alicea and Sharma, {Apurwa M.} and Miller, {Timothy M.} and Diamond, {Marc I.}",
note = "Funding Information: We thank Ann McKee, Bill Seeley, and Lea Grinberg for providing invaluable reagents for this study. We thank Peter Davies for providing MC1 antibody. We thank Matthew Brier, Jennifer Furman, Brandon Holmes, Suzanne Schindler, and Niall Prendergast for providing guidance and critiques during the preparation of this manuscript. This work was funded by NIH/NIA grant F30AG048653 (S.K.K.); NIH grant F31NS086251 (D.W.S.); NIH/NIA R01AG048678 , NIH/NINDS R01NS071835 , the Tau Consortium , and the Cure Alzheimer{\textquoteright}s Fund (M.I.D.). This work was supported by the Hope Center Alafi Neuroimaging Laboratory at Washington University in St. Louis , Neuro-Models Facility , Whole Brain Microscopy Facility , Moody Foundation Flow Cytometry Facility , and High Throughput Screening Core at University of Texas Southwestern . Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",
year = "2016",
month = nov,
day = "23",
doi = "10.1016/j.neuron.2016.09.055",
language = "English",
volume = "92",
pages = "796--812",
journal = "Neuron",
issn = "0896-6273",
number = "4",
}