title: Huntington's disease is a four-repeat tauopathy with tau nuclear rods.
abstract: An imbalance of tau isoforms containing either three or four microtubule-binding repeats causes frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) in families with intronic mutations in the MAPT gene. Here we report equivalent imbalances at the mRNA and protein levels and increased total tau levels in the brains of subjects with Huntington's disease (HD) together with rod-like tau deposits along neuronal nuclei. These tau nuclear rods show an ordered filamentous ultrastructure and can be found filling the neuronal nuclear indentations previously reported in HD brains. Finally, alterations in serine/arginine-rich splicing factor-6 coincide with tau missplicing, and a role of tau in HD pathogenesis is evidenced by the attenuation of motor abnormalities of mutant HTT transgenic mice in tau knockout backgrounds.
authors.affiliation: 1] Center for Molecular Biology "Severo Ochoa" (CBMSO) Consejo Superior de Investigaciones Científicas y Universidad Autónoma de Madrid (CSIC/UAM), Madrid, Spain. [2] Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Fernández-Nogales
authors.affiliation: 1] Center for Molecular Biology "Severo Ochoa" (CBMSO) Consejo Superior de Investigaciones Científicas y Universidad Autónoma de Madrid (CSIC/UAM), Madrid, Spain. [2] Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Spain. [3].
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Cabrera
authors.affiliation: 1] Center for Molecular Biology "Severo Ochoa" (CBMSO) Consejo Superior de Investigaciones Científicas y Universidad Autónoma de Madrid (CSIC/UAM), Madrid, Spain. [2] Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Spain. [3].
authors.forename: María
authors.initials: M
authors.lastname: Santos-Galindo
authors.affiliation: Department of Pathology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Jeroen J M
authors.initials: JJ
authors.lastname: Hoozemans
authors.affiliation: 1] Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Spain. [2] Institute of Neuropathology, Bellvitge Biomedical Research Institute (IDIBELL)-University Hospital Bellvitge, University of Barcelona, Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Isidro
authors.initials: I
authors.lastname: Ferrer
authors.affiliation: Department of Pathology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Annemieke J M
authors.initials: AJ
authors.lastname: Rozemuller
authors.affiliation: 1] Center for Molecular Biology "Severo Ochoa" (CBMSO) Consejo Superior de Investigaciones Científicas y Universidad Autónoma de Madrid (CSIC/UAM), Madrid, Spain. [2] Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Spain.
authors.forename: Félix
authors.initials: F
authors.lastname: Hernández
authors.affiliation: 1] Center for Molecular Biology "Severo Ochoa" (CBMSO) Consejo Superior de Investigaciones Científicas y Universidad Autónoma de Madrid (CSIC/UAM), Madrid, Spain. [2] Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Avila
authors.affiliation: 1] Center for Molecular Biology "Severo Ochoa" (CBMSO) Consejo Superior de Investigaciones Científicas y Universidad Autónoma de Madrid (CSIC/UAM), Madrid, Spain. [2] Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Spain.
authors.forename: José J
authors.initials: JJ
authors.lastname: Lucas
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001921:Brain / Q000473:pathology; D057180:Frontotemporal Dementia / Q000235:genetics*; D006801:Humans; D006816:Huntington Disease / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000068103:Serine-Arginine Splicing Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D024801:Tauopathies / Q000235:genetics / Q000378:metabolism*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: C054369:MAPT protein, human; D009687:Nuclear Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C489470:SRSF6 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D016875:tau Proteins; D000068103:Serine-Arginine Splicing Factors