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J Neuropathol Exp Neurol. 2017 Jul 1;76(7):605-619. doi: 10.1093/jnen/nlx041.

Multisite Assessment of Aging-Related Tau Astrogliopathy (ARTAG).

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Institute of Neurology, Medical University of Vienna, Vienna, Austria; Center for Neurodegenerative Disease Research, Institute on Aging and Department of Pathology and Laboratory Medicine of the Perelman School of Medicine at the University of Pennsylvania; and Department of Biostatistics and Epidemiology; and Department of Neurosurgery, Center for Brain Injury and Repair, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK; Department of Neuropathology, Institute of Pathology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida; Northwestern University Feinberg School of Medicine, Northwestern ADC Neuropathology Core, Chicago, Illinois; Clinical Neuropathology, King's College Hospital and London Neurodegenerative Brain Bank, London, UK; Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland; University of California San Francisco, Institute for Neurodegenerative Diseases, San Francisco, California; Neuropathology Department, Hôpital de La Salpetrière, AP-HP, UPMC-Sorbonne-University, Paris, France; Institute of Neuropathology, Bellvitge University Hospital, University of Barcelona, CIBERNED, Hospitalet de Llobregat, Barcelona, Spain; Discipline of Pathology, Sydney Medical School, The University of Sydney, Sydney, Australia; Neurological Tissue Bank of the Biobank-Hospital Clinic-IDIBAPS, Institut d'Investigacions Biomediques Pi i, Barcelona, Spain; Department of Medicine, Imperial College London, London, UK; IRCCS Foundation "Carlo Besta" Neurological Institute, Milan, Italy; Memory and Aging Center, Department of Neurology, University of California, San Francisco, California; Department of Pathology, University of Sao Paulo Medical School, LIM, São Paulo, Brazil; Brain & Mind Centre, Sydney Medical School, The University of Sydney, and UNSW Medicine & NeuRA, Sydney, Australia; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas; 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, New York; Department of Neuropathology, John Radcliffe Hospital, Oxford, UK; Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK; Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Mental Health and Psychiatry, University Hospitals and University of Geneva School of Medicine, Geneva, Switzerland; Institute of Clinical Neurosciences, University of Bristol, Learning & Research Level 2, Southmead Hospital, Bristol, UK; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada; Department of Pathology and Molecular Medicine, Thomayer Hospital, Prague, Czech Republic; Department of Pathology, First Medical Faculty, Charles University, Prague, Czech Republic; Department of Anatomical Pathology, Alfred Hospital , Prahran, Victoria, Australia; Division of Pathology, St. Michael's Hospital, Toronto, Ontario, Canada; Department of Pathology and Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky; Physiopathology in Aging Lab/Brazilian Aging Brain Study Group-LIM22, University of Sao Paulo Medical School, Sao Paulo, Brazil; Behavioral and Cognitive Neurology Unit, Department of Neurology, University of São Paulo , São Paulo, Brazil; Netherlands Brainbank, Amsterdam and Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands; Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan; Institute of Neuroanatomy, Centre for Biomedicine and Medical Technology Mannheim, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany; Department of Neurodegenerative Diseases and Gerontopsychiatry at the University of Bonn Medical Center, Bonn, Germany; Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan; Department of Neurology, Saitama Medical University International Medical Center, Saitama, Japan; Department of Neuroscience, Katholieke Universiteit-Leuven; and Department of Pathology, Universitaire Ziekenhuizen-Leuven, Leuven, Belgium; Laboratory of Neuropathology, Department of Pathology and Neuropathology, Kepler University Hospital, Medical School, Johannes Kepler University, Linz, Austria; Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK; and Department of Pathology and Laboratory Medicine, Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, University of Ottawa, Ontario, Canada.


Aging-related tau astrogliopathy (ARTAG) is a recently introduced terminology. To facilitate the consistent identification of ARTAG and to distinguish it from astroglial tau pathologies observed in the primary frontotemporal lobar degeneration tauopathies we evaluated how consistently neuropathologists recognize (1) different astroglial tau immunoreactivities, including those of ARTAG and those associated with primary tauopathies (Study 1); (2) ARTAG types (Study 2A); and (3) ARTAG severity (Study 2B). Microphotographs and scanned sections immunostained for phosphorylated tau (AT8) were made available for download and preview. Percentage of agreement and kappa values with 95% confidence interval (CI) were calculated for each evaluation. The overall agreement for Study 1 was >60% with a kappa value of 0.55 (95% CI 0.433-0.645). Moderate agreement (>90%, kappa 0.48, 95% CI 0.457-0.900) was reached in Study 2A for the identification of ARTAG pathology for each ARTAG subtype (kappa 0.37-0.72), whereas fair agreement (kappa 0.40, 95% CI 0.341-0.445) was reached for the evaluation of ARTAG severity. The overall assessment of ARTAG showed moderate agreement (kappa 0.60, 95% CI 0.534-0.653) among raters. Our study supports the application of the current harmonized evaluation strategy for ARTAG with a slight modification of the evaluation of its severity.


ARTAG; Aging; Digital pathology; Interrater agreement; Neuropathology; Tau; Tau-astrogliopathy

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