title: Tau prions from Alzheimer's disease and chronic traumatic encephalopathy patients propagate in cultured cells.
abstract: Tau prions are thought to aggregate in the central nervous system, resulting in neurodegeneration. Among the tauopathies, Alzheimer's disease (AD) is the most common, whereas argyrophilic grain disease (AGD), corticobasal degeneration (CBD), 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 AGD, 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 demonstrated that prion propagation in HEK cells requires isoform pairing between the infecting prion and the recipient substrate. Interestingly, tau aggregates in AD and CTE, containing both 3R and 4R 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. These results allowed us to determine the levels of tau prions in AD and CTE brain extracts.
authors.affiliation: Institute for Neurodegenerative Diseases, Weill Institute for Neurosciences, University of California, San Francisco, CA 94143.|Department of Neurology, University of California, San Francisco, CA 94143.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Woerman
authors.affiliation: Institute for Neurodegenerative Diseases, Weill Institute for Neurosciences, University of California, San Francisco, CA 94143.|Daiichi Sankyo Co., Ltd., Tokyo 140-8710, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Aoyagi
authors.affiliation: Institute for Neurodegenerative Diseases, Weill Institute for Neurosciences, University of California, San Francisco, CA 94143.
authors.forename: Smita
authors.initials: S
authors.lastname: Patel
authors.affiliation: Institute for Neurodegenerative Diseases, Weill Institute for Neurosciences, University of California, San Francisco, CA 94143.
authors.forename: Sabeen A
authors.initials: SA
authors.lastname: Kazmi
authors.affiliation: Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94143.
authors.forename: Iryna
authors.initials: I
authors.lastname: Lobach
authors.affiliation: Department of Neurology, University of California, San Francisco, CA 94143.|Department of Pathology, University of California, San Francisco, CA 94143.
authors.forename: Lea T
authors.initials: LT
authors.lastname: Grinberg
authors.affiliation: Chronic Traumatic Encephalopathy Program, Alzheimer's Disease Center, Boston University School of Medicine, Boston, MA 02118.|Department of Neurology, Boston University School of Medicine, Boston, MA 02118.|Department of Pathology, Boston University School of Medicine, Boston, MA 02118.|Veterans Affairs Boston Healthcare System, US Department of Veterans Affairs, Jamaica Plain, MA 02130.|US Department of Veterans Affairs Medical Center, Bedford, MA 01730.
authors.forename: Ann C
authors.initials: AC
authors.lastname: McKee
authors.affiliation: Department of Neurology, University of California, San Francisco, CA 94143.|Department of Pathology, University of California, San Francisco, CA 94143.
authors.forename: William W
authors.initials: WW
authors.lastname: Seeley
authors.affiliation: Institute for Neurodegenerative Diseases, Weill Institute for Neurosciences, University of California, San Francisco, CA 94143.|Department of Neurology, University of California, San Francisco, CA 94143.
authors.forename: Steven H
authors.initials: SH
authors.lastname: Olson
authors.affiliation: Institute for Neurodegenerative Diseases, Weill Institute for Neurosciences, University of California, San Francisco, CA 94143; stanley.prusiner@ucsf.edu.|Department of Neurology, University of California, San Francisco, CA 94143.|Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143.
authors.forename: Stanley B
authors.initials: SB
authors.lastname: Prusiner
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D000070627:Chronic Traumatic Encephalopathy / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008164:Luminescent Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D020774:Pick Disease of the Brain / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013494:Supranuclear Palsy, Progressive / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D016875:tau Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D008164:Luminescent Proteins; C054369:MAPT protein, human; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D016875:tau Proteins; C054562:yellow fluorescent protein, Bacteria
keywords: Pick’s disease; argyrophilic grain disease; corticobasal degeneration; progressive supranuclear palsy; tauopathies