Format

Send to

Choose Destination
Acta Neuropathol. 2016 Jan;131(1):87-102. doi: 10.1007/s00401-015-1509-x. Epub 2015 Dec 10.

Aging-related tau astrogliopathy (ARTAG): harmonized evaluation strategy.

Author information

1
Institute of Neurology, Medical University of Vienna, AKH 4J, Währinger Gürtel 18-20, 1097, Vienna, Austria. gabor.kovacs@meduniwien.ac.at.
2
Institute of Neuropathology, Bellvitge University Hospital, University of Barcelona, Hospitalet de Llobregat, Barcelona, Spain.
3
Department of Neurology, Memory and Aging Center, University of California, San Francisco, USA.
4
Department of Pathology, LIM-22, University of Sao Paulo Medical School, Sao Paulo, Brazil.
5
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
6
Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.
7
Institute of Neuropathology, University Hospital Zürich, Zurich, Switzerland.
8
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
9
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.
10
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.
11
Neuropathology Department, Hopital de La Salpetrière, AP-HP, UPMC-Sorbonne-University, Paris, France.
12
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
13
GMH-Neuroscience Research Australia and the University of New South Wales, Sydney, NSW, Australia.
14
Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
15
Institute of Clinical Neurosciences, University of Bristol, Learning and Research Level 2, Southmead Hospital, Bristol, UK.
16
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.
17
Division of Pathology, St. Michael's Hospital, 30 Bond St, Toronto, ON, Canada.
18
Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
19
Department of Pathology and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, 40536, USA.
20
Department of Pathology, Brain Research Institute, Niigata University, Niigata, 951-8585, Japan.
21
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.
22
Department of Neuropathology, John Radcliffe Hospital, Oxford, UK.
23
Department of Psychiatry and Psychotherapy, Centre for Neuropathology and Prion Research, Ludwig-Maximilians-University Munich, Munich, Germany.
24
Department of Neuropathology, Walton Centre, Liverpool, UK.
25
Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, AZ, 85351, USA.
26
Northwestern ADC Neuropathology Core, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
27
Clinical Neuropathology, King's College Hospital, London Neurodegenerative Brain Bank, London, UK.
28
Institute for Neurodegenerative Diseases, University of California San Francisco, San Francisco, CA, USA.
29
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
30
Neurological Tissue Bank of the Biobank-Hospital Clinic-IDIBAPS, Institut d'Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain.
31
Department of Medicine, Imperial College London, London, UK.
32
IRCCS Foundation "Carlo Besta" Neurological Institute, Milan, Italy.
33
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
34
Department of Neuropathology, Faculty of Medicine, Institute of Pathology, University of Debrecen, Nagyerdei krt. 98, 4032, Debrecen, Hungary.
35
Institute of Clinical Neurobiology, Alberichgasse 5/13, 1150, Vienna, Austria.
36
Department of Neurology and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, 40536, USA.
37
Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK.
38
Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
39
Department of Mental Health and Psychiatry, University Hospitals and University of Geneva School of Medicine, Geneva, Switzerland.
40
Discipline of Pathology, Sydney Medical School, The University of Sydney, Sydney, NSW, 2006, Australia.
41
Institute of Brain, Behaviour and Mental Health, Manchester University Faculty of Medical and Health Sciences, Manchester, UK.
42
Department of Pathology and Molecular Medicine, Thomayer Hospital, Prague 4, Czech Republic.
43
Department of Neurology and Pathology, Boston University School of Medicine and VA Healthcare System, Boston, MA, 02118, USA.
44
Department of Anatomical Pathology, Alfred Hospital, Prahran, VIC, 3004, Australia.
45
Institute of Neurology, Medical University of Vienna, AKH 4J, Währinger Gürtel 18-20, 1097, Vienna, Austria.
46
Department of Neurology, Medical University of Vienna, Vienna, Austria.
47
Department of Pathology, University of Washington, Seattle, WA, USA.
48
Department of Neuropathology (The Brain Bank for Aging Research), Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan.
49
Physiopathology in Aging Lab/Brazilian Aging Brain Study Group-LIM22, University of Sao Paulo Medical School, Sao Paulo, Brazil.
50
Netherlands Brainbank and Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
51
Department of Pathology, Rush University Medical Center, Chicago, IL, USA.
52
Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
53
Institute of Neuroanatomy, Centre for Biomedicine and Medical Technology Mannheim, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.
54
Department of Neurology, Saitama Medical University International Medical Center, Saitama, Japan.
55
Laboratory of Neuropathology, Institute of Pathology, University of Ulm, 89081, Ulm, Germany.
56
Department of Neuroscience, KU-Leuven, 3000, Louvain, Belgium.
57
Institute of Pathology, University Hospital Basel, Basel, Switzerland.
58
Division of Neuropathology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
59
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.
60
Department of Neurology, Brain Research Institute, University of California, Los Angeles (UCLA) Medical Center and David Geffen School of Medicine, Los Angeles, CA, USA.
61
Department of Pathology and Neuropathology, Laboratory of Neuropathology, Neuromed Campus, Kepler University Hospital, Medical School, Johannes Kepler University, Linz, Austria.
62
Department of Neurology, Center for Cognitive Neurology, New York University School of Medicine, ERSP, 450 East 29th Street, New York, NY, 10016, USA.
63
Department of Pathology, Center for Cognitive Neurology, New York University School of Medicine, ERSP, 450 East 29th Street, New York, NY, 10016, USA.
64
Department of Psychiatry, Center for Cognitive Neurology, New York University School of Medicine, ERSP, 450 East 29th Street, New York, NY, 10016, USA.
65
Department of Pathology and Laboratory Medicine, Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada.
66
Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
67
Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA. dickson.dennis@mayo.edu.

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.

KEYWORDS:

ARTAG; Aging; Tau; Tau astrogliopathy

PMID:
26659578
PMCID:
PMC4879001
DOI:
10.1007/s00401-015-1509-x
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substance, Grant support

Publication types

MeSH terms

Substance

Grant support

Supplemental Content

Full text links

Icon for Springer Icon for PubMed Central
Loading ...
Support Center