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.

Centre for Clinical Brain Sciences University of Edinburgh Edinburgh UK

Civin Laboratory for Neuropathology Banner Sun Health Research Institute Sun City AZ 85351 USA

Clinical Neuropathology King's College Hospital London Neurodegenerative Brain Bank London UK

Department of Anatomical Pathology Alfred Hospital Prahran VIC 3004 Australia

Department of Immunology Genetics and Pathology Uppsala University Uppsala Sweden

Department of Medicine Imperial College London London UK

Department of Mental Health and Psychiatry University Hospitals and University of Geneva School of Medicine Geneva Switzerland

Department of Neurological Sciences Rush University Medical Center Chicago IL USA

Department of Neurology and Neurobiology of Aging Kanazawa University Graduate School of Medical Sciences Kanazawa Japan

Department of Neurology and Pathology Boston University School of Medicine and VA Healthcare System Boston MA 02118 USA

Department of Neurology and Sanders Brown Center on Aging University of Kentucky Lexington KY 40536 USA

Department of Neurology Brain Research Institute University of California Los Angeles Medical Center and David Geffen School of Medicine Los Angeles CA USA

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 Neurology Medical University of Vienna Vienna Austria

Department of Neurology Memory and Aging Center University of California San Francisco USA

Department of Neurology Saitama Medical University International Medical Center Saitama Japan

Department of Neuropathology Faculty of Medicine Institute of Pathology University of Debrecen Nagyerdei krt 98 4032 Debrecen Hungary

Department of Neuropathology John Radcliffe Hospital Oxford UK

Department of Neuropathology Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology Tokyo Japan

Department of Neuropathology Walton Centre Liverpool UK

Department of Neuroscience KU Leuven 3000 Louvain Belgium

Department of Neuroscience Mayo Clinic 4500 San Pablo Road Jacksonville FL 32224 USA

Department of Pathology and Immunology Washington University School of Medicine St Louis MO USA

Department of Pathology and Laboratory Medicine Centre for Cancer Therapeutics Ottawa Hospital Research Institute University of Ottawa Ottawa Canada

Department of Pathology and Laboratory Medicine Indiana University School of Medicine Indianapolis IN USA

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

Department of Pathology and Laboratory Medicine University of British Columbia Vancouver Canada

Department of Pathology and Molecular Medicine Thomayer Hospital Prague 4 Czech Republic

Department of Pathology and Neuropathology Laboratory of Neuropathology Neuromed Campus Kepler University Hospital Medical School Johannes Kepler University Linz Austria

Department of Pathology and Sanders Brown Center on Aging University of Kentucky Lexington KY 40536 USA

Department of Pathology Brain Research Institute Niigata University Niigata 951 8585 Japan

Department of Pathology Brigham and Women's Hospital Harvard Medical School Boston MA 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 Pathology Friedman Brain Institute and the Ronald M Loeb Center for Alzheimer's Disease Icahn School of Medicine at Mount Sinai New York USA

Department of Pathology LIM 22 University of Sao Paulo Medical School Sao Paulo Brazil

Department of Pathology Rush University Medical Center Chicago IL USA

Department of Pathology University of Pittsburgh Pittsburgh PA USA

Department of Pathology University of Texas Southwestern Medical Center Dallas TX USA

Department of Pathology University of Washington Seattle WA USA

Department of Psychiatry and Psychotherapy Centre for Neuropathology and Prion Research Ludwig Maximilians University Munich Munich Germany

Department of Psychiatry Center for Cognitive Neurology New York University School of Medicine ERSP 450 East 29th Street New York NY 10016 USA

Discipline of Pathology Sydney Medical School The University of Sydney Sydney NSW 2006 Australia

Division of Neuropathology Department of Pathology Johns Hopkins University School of Medicine Baltimore MD USA

Division of Pathology St Michael's Hospital 30 Bond St Toronto ON Canada

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

GMH Neuroscience Research Australia and the University of New South Wales Sydney NSW Australia

Institute for Neurodegenerative Diseases University of California San Francisco San Francisco CA USA

Institute of Brain Behaviour and Mental Health Manchester University Faculty of Medical and Health Sciences Manchester UK

Institute of Clinical Neurobiology Alberichgasse 5 13 1150 Vienna Austria

Institute of Clinical Neurosciences University of Bristol Learning and Research Level 2 Southmead Hospital Bristol UK

Institute of Neuroanatomy Centre for Biomedicine and Medical Technology Mannheim Medical Faculty Mannheim Heidelberg University Heidelberg Germany

Institute of Neurology Medical University of Vienna AKH 4J Währinger Gürtel 18 20 1097 Vienna Austria

Institute of Neuropathology Bellvitge University Hospital University of Barcelona Hospitalet de Llobregat Barcelona Spain

Institute of Neuropathology University Hospital Zürich Zurich Switzerland

Institute of Neuroscience Newcastle University Newcastle upon Tyne UK

Institute of Pathology University Hospital Basel Basel Switzerland

IRCCS Foundation Carlo Besta Neurological Institute Milan Italy

Laboratory of Neuropathology Institute of Pathology University of Ulm 89081 Ulm Germany

Netherlands Brainbank and Department of Pathology VU University Medical Center Amsterdam The Netherlands

Neurological Tissue Bank of the Biobank Hospital Clinic IDIBAPS Institut d'Investigacions Biomediques August Pi i Sunyer Barcelona Spain

Neuropathology Department Hopital de La Salpetrière AP HP UPMC Sorbonne University Paris France

Northwestern ADC Neuropathology Core Northwestern University Feinberg School of Medicine Chicago IL USA

Physiopathology in Aging Lab Brazilian Aging Brain Study Group LIM22 University of Sao Paulo Medical School Sao Paulo Brazil

Section of Neuropathology Department of Pathology and Laboratory Medicine Brain Research Institute University of California Los Angeles Medical Center and David Geffen School of Medicine Los Angeles CA USA

Sheffield Institute for Translational Neuroscience University of Sheffield Sheffield UK

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Comorbid Neurodegeneration in Primary Progressive Aphasia: Clinicopathological Correlations in a Single-Center Study

PART and ARTAG tauopathies at a relatively young age as a concomitant finding in sporadic Creutzfeldt-Jakob disease

Pyramidal system involvement in progressive supranuclear palsy - a clinicopathological correlation

Multisite Assessment of Aging-Related Tau Astrogliopathy (ARTAG)