title: Aging-related tau astrogliopathy (ARTAG): harmonized evaluation strategy.
abstract: Pathological accumulation of abnormally phosphorylated tau protein in astrocytes is a frequent, but poorly characterized feature of the aging brain. Its etiology is uncertain, but its presence is sufficiently ubiquitous to merit further characterization and classification, which may stimulate clinicopathological studies and research into its pathobiology. This paper aims to harmonize evaluation and nomenclature of aging-related tau astrogliopathy (ARTAG), a term that refers to a morphological spectrum of astroglial pathology detected by tau immunohistochemistry, especially with phosphorylation-dependent and 4R isoform-specific antibodies. ARTAG occurs mainly, but not exclusively, in individuals over 60 years of age. Tau-immunoreactive astrocytes in ARTAG include thorn-shaped astrocytes at the glia limitans and in white matter, as well as solitary or clustered astrocytes with perinuclear cytoplasmic tau immunoreactivity that extends into the astroglial processes as fine fibrillar or granular immunopositivity, typically in gray matter. Various forms of ARTAG may coexist in the same brain and might reflect different pathogenic processes. Based on morphology and anatomical distribution, ARTAG can be distinguished from primary tauopathies, but may be concurrent with primary tauopathies or other disorders. We recommend four steps for evaluation of ARTAG: (1) identification of five types based on the location of either morphologies of tau astrogliopathy: subpial, subependymal, perivascular, white matter, gray matter; (2) documentation of the regional involvement: medial temporal lobe, lobar (frontal, parietal, occipital, lateral temporal), subcortical, brainstem; (3) documentation of the severity of tau astrogliopathy; and (4) description of subregional involvement. Some types of ARTAG may underlie neurological symptoms; however, the clinical significance of ARTAG is currently uncertain and awaits further studies. The goal of this proposal is to raise awareness of astroglial tau pathology in the aged brain, facilitating communication among neuropathologists and researchers, and informing interpretation of clinical biomarkers and imaging studies that focus on tau-related indicators.
authors.affiliation: Institute of Neurology, Medical University of Vienna, AKH 4J, Währinger Gürtel 18-20, 1097, Vienna, Austria. gabor.kovacs@meduniwien.ac.at.
authors.forename: Gabor G
authors.initials: GG
authors.lastname: Kovacs
authors.affiliation: Institute of Neuropathology, Bellvitge University Hospital, University of Barcelona, Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Isidro
authors.initials: I
authors.lastname: Ferrer
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California, San Francisco, USA.|Department of Pathology, LIM-22, University of Sao Paulo Medical School, Sao Paulo, Brazil.
authors.forename: Lea T
authors.initials: LT
authors.lastname: Grinberg
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Irina
authors.initials: I
authors.lastname: Alafuzoff
authors.affiliation: Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Johannes
authors.initials: J
authors.lastname: Attems
authors.affiliation: Institute of Neuropathology, University Hospital Zürich, Zurich, Switzerland.
authors.forename: Herbert
authors.initials: H
authors.lastname: Budka
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Cairns
authors.affiliation: Department of Pathology, Friedman Brain Institute, and the Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, USA.|Fishberg Department of Neuroscience, Friedman Brain Institute, and Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: Crary
authors.affiliation: Neuropathology Department, Hopital de La Salpetrière, AP-HP, UPMC-Sorbonne-University, Paris, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Duyckaerts
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Bernardino
authors.initials: B
authors.lastname: Ghetti
authors.affiliation: GMH-Neuroscience Research Australia and the University of New South Wales, Sydney, NSW, Australia.
authors.forename: Glenda M
authors.initials: GM
authors.lastname: Halliday
authors.affiliation: Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
authors.forename: James W
authors.initials: JW
authors.lastname: Ironside
authors.affiliation: Institute of Clinical Neurosciences, University of Bristol, Learning and Research Level 2, Southmead Hospital, Bristol, UK.
authors.forename: Seth
authors.initials: S
authors.lastname: Love
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: Ian R
authors.initials: IR
authors.lastname: Mackenzie
authors.affiliation: Division of Pathology, St. Michael's Hospital, 30 Bond St, Toronto, ON, Canada.
authors.forename: David G
authors.initials: DG
authors.lastname: Munoz
authors.affiliation: Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Murray
authors.affiliation: Department of Pathology and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, 40536, USA.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Nelson
authors.affiliation: Department of Pathology, Brain Research Institute, Niigata University, Niigata, 951-8585, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Pathology and Laboratory Medicine of the Perelman School of Medicine, Center for Neurodegenerative Disease Research, Institute On Aging, University of Pennsylvania, Philadelphia, USA.
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.affiliation: Department of Neuropathology, John Radcliffe Hospital, Oxford, UK.
authors.forename: Olaf
authors.initials: O
authors.lastname: Ansorge
authors.affiliation: Department of Psychiatry and Psychotherapy, Centre for Neuropathology and Prion Research, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Arzberger
authors.affiliation: Department of Neuropathology, Walton Centre, Liverpool, UK.
authors.forename: Atik
authors.initials: A
authors.lastname: Baborie
authors.affiliation: Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, AZ, 85351, USA.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Beach
authors.affiliation: Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
authors.forename: Kevin F
authors.initials: KF
authors.lastname: Bieniek
authors.affiliation: Northwestern ADC Neuropathology Core, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Eileen H
authors.initials: EH
authors.lastname: Bigio
authors.affiliation: Clinical Neuropathology, King's College Hospital, London Neurodegenerative Brain Bank, London, UK.
authors.forename: Istvan
authors.initials: I
authors.lastname: Bodi
authors.affiliation: Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, AZ, 85351, USA.|Institute for Neurodegenerative Diseases, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Brittany N
authors.initials: BN
authors.lastname: Dugger
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Mel
authors.initials: M
authors.lastname: Feany
authors.affiliation: Neurological Tissue Bank of the Biobank-Hospital Clinic-IDIBAPS, Institut d'Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain.
authors.forename: Ellen
authors.initials: E
authors.lastname: Gelpi
authors.affiliation: Department of Medicine, Imperial College London, London, UK.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Gentleman
authors.affiliation: IRCCS Foundation "Carlo Besta" Neurological Institute, Milan, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Giaccone
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Kimmo J
authors.initials: KJ
authors.lastname: Hatanpaa
authors.affiliation: Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Heale
authors.affiliation: Fishberg Department of Neuroscience, Friedman Brain Institute, and Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Hof
authors.affiliation: Department of Neuropathology, John Radcliffe Hospital, Oxford, UK.
authors.forename: Monika
authors.initials: M
authors.lastname: Hofer
authors.affiliation: Department of Neuropathology, Faculty of Medicine, Institute of Pathology, University of Debrecen, Nagyerdei krt. 98, 4032, Debrecen, Hungary.
authors.forename: Tibor
authors.initials: T
authors.lastname: Hortobágyi
authors.affiliation: Institute of Clinical Neurobiology, Alberichgasse 5/13, 1150, Vienna, Austria.
authors.forename: Kurt
authors.initials: K
authors.lastname: Jellinger
authors.affiliation: Department of Neurology and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, 40536, USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Jicha
authors.affiliation: Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Ince
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Kofler
authors.affiliation: Department of Mental Health and Psychiatry, University Hospitals and University of Geneva School of Medicine, Geneva, Switzerland.
authors.forename: Enikö
authors.initials: E
authors.lastname: Kövari
authors.affiliation: Discipline of Pathology, Sydney Medical School, The University of Sydney, Sydney, NSW, 2006, Australia.
authors.forename: Jillian J
authors.initials: JJ
authors.lastname: Kril
authors.affiliation: Institute of Brain, Behaviour and Mental Health, Manchester University Faculty of Medical and Health Sciences, Manchester, UK.
authors.forename: David M
authors.initials: DM
authors.lastname: Mann
authors.affiliation: Department of Pathology and Molecular Medicine, Thomayer Hospital, Prague 4, Czech Republic.
authors.forename: Radoslav
authors.initials: R
authors.lastname: Matej
authors.affiliation: Department of Neurology and Pathology, Boston University School of Medicine and VA Healthcare System, Boston, MA, 02118, USA.
authors.forename: Ann C
authors.initials: AC
authors.lastname: McKee
authors.affiliation: Department of Anatomical Pathology, Alfred Hospital, Prahran, VIC, 3004, Australia.
authors.forename: Catriona
authors.initials: C
authors.lastname: McLean
authors.affiliation: Institute of Neurology, Medical University of Vienna, AKH 4J, Währinger Gürtel 18-20, 1097, Vienna, Austria.|Department of Neurology, Medical University of Vienna, Vienna, Austria.
authors.forename: Ivan
authors.initials: I
authors.lastname: Milenkovic
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Montine
authors.affiliation: Department of Neuropathology (The Brain Bank for Aging Research), Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Murayama
authors.affiliation: Department of Pathology and Laboratory Medicine of the Perelman School of Medicine, Center for Neurodegenerative Disease Research, Institute On Aging, University of Pennsylvania, Philadelphia, USA.
authors.forename: Edward B
authors.initials: EB
authors.lastname: Lee
authors.affiliation: Institute of Neurology, Medical University of Vienna, AKH 4J, Währinger Gürtel 18-20, 1097, Vienna, Austria.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Rahimi
authors.affiliation: Physiopathology in Aging Lab/Brazilian Aging Brain Study Group-LIM22, University of Sao Paulo Medical School, Sao Paulo, Brazil.
authors.forename: Roberta D
authors.initials: RD
authors.lastname: Rodriguez
authors.affiliation: Netherlands Brainbank and Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Annemieke
authors.initials: A
authors.lastname: Rozemüller
authors.affiliation: Department of Pathology, Rush University Medical Center, Chicago, IL, USA.|Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Schneider
authors.affiliation: Institute of Neuroanatomy, Centre for Biomedicine and Medical Technology Mannheim, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schultz
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California, San Francisco, USA.
authors.forename: William
authors.initials: W
authors.lastname: Seeley
authors.affiliation: Neuropathology Department, Hopital de La Salpetrière, AP-HP, UPMC-Sorbonne-University, Paris, France.
authors.forename: Danielle
authors.initials: D
authors.lastname: Seilhean
authors.affiliation: Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
authors.forename: Colin
authors.initials: C
authors.lastname: Smith
authors.affiliation: IRCCS Foundation "Carlo Besta" Neurological Institute, Milan, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Tagliavini
authors.affiliation: Department of Neurology, Saitama Medical University International Medical Center, Saitama, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Takao
authors.affiliation: Laboratory of Neuropathology, Institute of Pathology, University of Ulm, 89081, Ulm, Germany.|Department of Neuroscience, KU-Leuven, 3000, Louvain, Belgium.
authors.forename: Dietmar Rudolf
authors.initials: DR
authors.lastname: Thal
authors.affiliation: Department of Pathology and Laboratory Medicine of the Perelman School of Medicine, Center for Neurodegenerative Disease Research, Institute On Aging, University of Pennsylvania, Philadelphia, USA.
authors.forename: Jon B
authors.initials: JB
authors.lastname: Toledo
authors.affiliation: Institute of Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Tolnay
authors.affiliation: Division of Neuropathology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Troncoso
authors.affiliation: Section of Neuropathology, Department of Pathology and Laboratory Medicine, Brain Research Institute, University of California, Los Angeles (UCLA) Medical Center and David Geffen School of Medicine, Los Angeles, CA, USA.|Department of Neurology, Brain Research Institute, University of California, Los Angeles (UCLA) Medical Center and David Geffen School of Medicine, Los Angeles, CA, USA.
authors.forename: Harry V
authors.initials: HV
authors.lastname: Vinters
authors.affiliation: Department of Pathology and Neuropathology, Laboratory of Neuropathology, Neuromed Campus, Kepler University Hospital, Medical School, Johannes Kepler University, Linz, Austria.
authors.forename: Serge
authors.initials: S
authors.lastname: Weis
authors.affiliation: Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Wharton
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Charles L
authors.initials: CL
authors.lastname: White
authors.affiliation: Department of Neurology, Center for Cognitive Neurology, New York University School of Medicine, ERSP, 450 East 29th Street, New York, NY, 10016, USA.|Department of Pathology, Center for Cognitive Neurology, New York University School of Medicine, ERSP, 450 East 29th Street, New York, NY, 10016, USA.|Department of Psychiatry, Center for Cognitive Neurology, New York University School of Medicine, ERSP, 450 East 29th Street, New York, NY, 10016, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wisniewski
authors.affiliation: Department of Pathology and Laboratory Medicine, Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada.
authors.forename: John M
authors.initials: JM
authors.lastname: Woulfe
authors.affiliation: Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Yamada
authors.affiliation: Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA. dickson.dennis@mayo.edu.
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
mesh_terms: D000375:Aging; D000818:Animals; D001253:Astrocytes / Q000166:cytology*; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D009457:Neuroglia / Q000473:pathology; D024801:Tauopathies / Q000378:metabolism / Q000473:pathology*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins
keywords: ARTAG; Aging; Tau; Tau astrogliopathy