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Propagation of tau prions from Alzheimer's disease and chronic traumatic encephalopathy patients in cultured cells
Author(s) -
Woerman Amanda L,
Aoyagi Atsushi,
Patel Smita,
Kazmi Sabeen A,
Lobach Iryna,
Grinberg Lea T,
McKee Ann C,
Seeley William W,
Olson Steven H,
Prusiner Stanley B
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.763.12
Subject(s) - hek 293 cells , chronic traumatic encephalopathy , gene isoform , tau protein , neurodegeneration , corticobasal degeneration , progressive supranuclear palsy , neuroscience , biology , disease , medicine , virology , pathology , alzheimer's disease , genetics , receptor , poison control , environmental health , injury prevention , concussion , gene
Tau prions aggregate in the central nervous system, giving rise to neurodegeneration. Among the tauopathies, Alzheimer's disease (AD) is the most common, whereas chronic traumatic encephalopathy (CTE), Pick's disease (PiD), and progressive supranuclear palsy (PSP) are less prevalent. Brain extracts from deceased individuals with PiD, a neurodegenerative disorder characterized by three‐repeat (3R) tau prions, were used to infect HEK293T cells expressing 3R tau fused to yellow fluorescent protein (YFP). Extracts from argyrophilic grain disease (AGD), corticobasal degeneration (CBD), and PSP patient samples, which contain four‐repeat (4R) tau prions, were transmitted to HEK293 cells expressing 4R tau fused to YFP. These studies demonstrate that prion propagation in HEK cells requires isoform pairing between the infecting prion and the recipient substrate. Interestingly, tau aggregates in AD and CTE, which contain both the 3R and 4R tau isoforms, were unable to robustly infect either 3R‐ or 4R‐expressing cells. However, AD and CTE prions were able to replicate in HEK293T cells expressing both 3R and 4R tau. Unexpectedly, increasing the level of 4R isoform expression alone supported the propagation of both AD and CTE prions. The finding that tau prion strains are isoform specific may have important implications for developing anti‐tau therapeutics and disease‐specific PET probes. Support or Funding Information This work was supported by NIH Grants AG002132 and AG031220, Daiichi Sankyo, Dana Foundation, Glenn Foundation, Sherman Fairchild Foundation, and a gift from the Rainwater Charitable Foundation. Control, AD, AGD, CBD, PiD, and PSP tissue samples were provided by the University of California, San Francisco, Neurodegenerative Disease Brain Bank, which is supported by NIH Grants AG023501 and AG19724 (to W.W.S.), Tau Consortium, and Consortium for Frontotemporal Dementia Research. CTE tissue samples were provided by the Boston University Alzheimer's Disease Center Chronic Traumatic Encephalopathy Center, which is supported by the Department of Veterans Affairs, National Institute of Neurological Disorders and Stroke, National Institute of Biomedical Imaging and Bioengineering (NS086559), National Institute on Aging, Boston University Alzheimer's Disease Center (AG13846; Supplement 0572063345–5), Concussion Legacy Foundation, Andlinger Foundation, and World Wrestling Entertainment, Inc.