1. A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer’s disease
- Author
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Barthélemy, Nicolas R, Li, Yan, Morris, John C, Neimeyer, Katie, Noble, James, Norton, Joanne, Perrin, Richard, Raichle, Marc, Renton, Alan, Ringman, John, Roh, Jee Hoon, Salloway, Stephen, Schofield, Peter, Karch, Celeste M, Shimada, Hiroyuki, Sigurdson, Wendy, Sohrabi, Hamid, Sparks, Paige, Suzuki, Kazushi, Taddei, Kevin, Wang, Peter, Xiong, Chengjie, Xu, Xiong, Allegri, Ricardo, Mendez, Patricio Chrem, Berman, Sarah B, Ikeuchi, Takeshi, Mori, Hiroshi, Shoji, Mikio, Joseph-Mathurin, Nelly, Farlow, Martin, Chhatwal, Jasmeer, Graff-Radford, Neill R, Schofield, Peter R, Masters, Colin L, Martins, Ralph N, O'Connor, Antoinette, Gordon, Brian A, Fox, Nick C, Levin, Johannes, Jucker, Mathias, Gabelle, Audrey, Lehmann, Sylvain, Sato, Chihiro, Bateman, Randall J, McDade, Eric, Network, Dominantly Inherited Alzheimer, Hassenstab, Jason, Bateman, Randy, Bechara, Jacob, Benzinger, Tammie, Berman, Sarah, Bodge, Courtney, Brandon, Susan, Brooks, William Bill, Buck, Jill, Buckles, Virginia, Chea, Sochenda, Benzinger, Tammie L S, Chrem Mendez, Patricio, Chui, Helena, Cinco, Jake, Clifford, Jack, Cruchaga, Carlos, Donahue, Tamara, Douglas, Jane, Edigo, Noelia, Erekin-Taner, Nilufer, Fagan, Anne, Fitzpatrick, Colleen, Flynn, Gigi, Fox, Nick, Franklin, Erin, Fujii, Hisako, Gant, Cortaiga, Gardener, Samantha, Ghetti, Bernardino, Fagan, Anne M, Goate, Alison, Goldman, Jill, Gordon, Brian, Graff-Radford, Neill, Gray, Julia, Groves, Alexander, Hoechst-Swisher, Laura, Holtzman, David, Hornbeck, Russ, Perrin, Richard J, DiBari, Siri Houeland, Ikonomovic, Snezana, Jerome, Gina, Karch, Celeste, Kasuga, Kensaku, Kawarabayashi, Takeshi, Klunk, William Bill, Koeppe, Robert, Kuder-Buletta, Elke, Goate, Alison M, Laske, Christoph, Lee, Jae-Hong, Martins, Ralph, Mason, Neal Scott, Masters, Colin, Maue-Dreyfus, Denise, Morris, John, Nagamatsu, Akem, Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia [Buenos Aires] (FLENI), FLENI, University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Niigata University, Osaka City University (OCU), Hirosaki University, The University of Tokyo (UTokyo), Columbia University [New York], Indiana University - Purdue University Indianapolis (IUPUI), Indiana University System, Harvard Medical School [Boston] (HMS), Mayo Clinic [Jacksonville], Brown University, Neuroscience Research Australia (NeuRA), University of New South Wales [Sydney] (UNSW), The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Edith Cowan University (ECU), Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO)-Planning and Transport Research Centre (PATREC), University College of London [London] (UCL), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Ludwig-Maximilians-Universität München (LMU), Munich Cluster for systems neurology [Munich] (SyNergy), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU), University of Tübingen, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), BioCampus Montpellier (BCM), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Dominantly Inherited Alzheimer Network: Ricardo Allegri, Randy Bateman, Jacob Bechara, Tammie Benzinger, Sarah Berman, Courtney Bodge, Susan Brandon, William Bill Brooks, Jill Buck, Virginia Buckles, Sochenda Chea, Jasmeer Chhatwal, Patricio Chrem Mendez, Helena Chui, Jake Cinco, Jack Clifford, Carlos Cruchaga, Tamara Donahue, Jane Douglas, Noelia Edigo, Nilufer Erekin-Taner, Anne Fagan, Martin Farlow, Colleen Fitzpatrick, Gigi Flynn, Nick Fox, Erin Franklin, Hisako Fujii, Cortaiga Gant, Samantha Gardener, Bernardino Ghetti, Alison Goate, Jill Goldman, Brian Gordon, Neill Graff-Radford, Julia Gray, Alexander Groves, Jason Hassenstab, Laura Hoechst-Swisher, David Holtzman, Russ Hornbeck, Siri Houeland DiBari, Takeshi Ikeuchi, Snezana Ikonomovic, Gina Jerome, Mathias Jucker, Celeste Karch, Kensaku Kasuga, Takeshi Kawarabayashi, William Bill Klunk, Robert Koeppe, Elke Kuder-Buletta, Christoph Laske, Jae-Hong Lee, Johannes Levin, Ralph Martins, Neal Scott Mason, Colin Masters, Denise Maue-Dreyfus, Eric McDade, Hiroshi Mori, John Morris, Akem Nagamatsu, Katie Neimeyer, James Noble, Joanne Norton, Richard Perrin, Marc Raichle, Alan Renton, John Ringman, Jee Hoon Roh, Stephen Salloway, Peter Schofield, Hiroyuki Shimada, Wendy Sigurdson, Hamid Sohrabi, Paige Sparks, Kazushi Suzuki, Kevin Taddei, Peter Wang, Chengjie Xiong, Xiong Xu, Technische Universität München [München] (TUM)-Ludwig-Maximilians-Universität München (LMU), BioCampus (BCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and Michel-Avella, Amandine
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0301 basic medicine ,Male ,[SDV]Life Sciences [q-bio] ,Inheritance Patterns ,genetics [Alzheimer Disease] ,Plaque, Amyloid ,Disease ,0302 clinical medicine ,Cerebrospinal fluid ,Cognition ,pathology [Brain] ,Phosphorylation ,biology ,Neurodegeneration ,Brain ,General Medicine ,Middle Aged ,Magnetic Resonance Imaging ,3. Good health ,[SDV] Life Sciences [q-bio] ,cerebrospinal fluid [Alzheimer Disease] ,030220 oncology & carcinogenesis ,Disease Progression ,Female ,Alzheimer's disease ,metabolism [Alzheimer Disease] ,Adult ,Amyloid ,genetics [Inheritance Patterns] ,Tau protein ,Neuroimaging ,tau Proteins ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,Atrophy ,Alzheimer Disease ,Fluorodeoxyglucose F18 ,mental disorders ,medicine ,Humans ,ddc:610 ,pathology [Plaque, Amyloid] ,chemistry [Fluorodeoxyglucose F18] ,metabolism [Amyloid] ,Aged ,medicine.disease ,metabolism [tau Proteins] ,030104 developmental biology ,cerebrospinal fluid [tau Proteins] ,Solubility ,biology.protein ,diagnostic imaging [Alzheimer Disease] ,Neuroscience - Abstract
International audience; Development of tau-based therapies for Alzheimer's disease requires an understanding of the timing of disease-related changes in tau. We quantified the phosphorylation state at multiple sites of the tau protein in cerebrospinal fluid markers across four decades of disease progression in dominantly inherited Alzheimer's disease. We identified a pattern of tau staging where site-specific phosphorylation changes occur at different periods of disease progression and follow distinct trajectories over time. These tau phosphorylation state changes are uniquely associated with structural, metabolic, neurodegenerative and clinical markers of disease, and some (p-tau217 and p-tau181) begin with the initial increases in aggregate amyloid-β as early as two decades before the development of aggregated tau pathology. Others (p-tau205 and t-tau) increase with atrophy and hypometabolism closer to symptom onset. These findings provide insights into the pathways linking tau, amyloid-β and neurodegeneration, and may facilitate clinical trials of tau-based treatments.
- Published
- 2020
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