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

Gabor G. Kovacs; Isidro Ferrer; Lea T. Grinberg; Irina Alafuzoff; Johannes Attems; Herbert Budka; Nigel J. Cairns; John F. Crary; Charles Duyckaerts; Bernardino Ghetti; Glenda M. Halliday; James W. Ironside; Seth Love; Ian R. Mackenzie; David G. Munoz; Melissa E. Murray; Peter T. Nelson; Hitoshi Takahashi; John Q. Trojanowski; Olaf Ansorge; Thomas Arzberger; Atik Baborie; Thomas G. Beach; Kevin F. Bieniek; Eileen H. Bigio; Istvan Bodi; Brittany N. Dugger; Mel Feany; Ellen Gelpi; Stephen M. Gentleman; Giorgio Giaccone; Kimmo J. Hatanpaa; Richard Heale; Patrick R. Hof; Monika Hofer; Tibor Hortobágyi; Kurt Jellinger; Gregory A. Jicha; Paul Ince; Julia Kofler; Enikö Kövari; Jillian J. Kril; David M. Mann; Radoslav Matej; Ann C. McKee; Catriona McLean; Ivan Milenkovic; Thomas J. Montine; Shigeo Murayama; Edward B. Lee; Jasmin Rahimi; Roberta D. Rodriguez; Annemieke Rozemüller; Julie A. Schneider; Christian Schultz; William Seeley; Danielle Seilhean; Colin Smith; Fabrizio Tagliavini; Masaki Takao; Dietmar Rudolf Thal; Jon B. Toledo; Markus Tolnay; Juan C. Troncoso; Harry V. Vinters; Serge Weis; Stephen B. Wharton; Charles L. White; Thomas Wisniewski; John M. Woulfe; Masahito Yamada; Dennis W. Dickson

doi:10.1007/s00401-015-1509-x

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

Gabor G. Kovacs, Isidro Ferrer, Lea T. Grinberg, Irina Alafuzoff, Johannes Attems, Herbert Budka, Nigel J. Cairns, John F. Crary, Charles Duyckaerts, Bernardino Ghetti, Glenda M. Halliday, James W. Ironside, Seth Love, Ian R. Mackenzie, David G. Munoz, Melissa E. Murray, Peter T. Nelson, Hitoshi Takahashi, John Q. Trojanowski, Olaf AnsorgeThomas Arzberger, Atik Baborie, Thomas G. Beach, Kevin F. Bieniek, Eileen H. Bigio, Istvan Bodi, Brittany N. Dugger, Mel Feany, Ellen Gelpi, Stephen M. Gentleman, Giorgio Giaccone, Kimmo J. Hatanpaa, Richard Heale, Patrick R. Hof, Monika Hofer, Tibor Hortobágyi, Kurt Jellinger, Gregory A. Jicha, Paul Ince, Julia Kofler, Enikö Kövari, Jillian J. Kril, David M. Mann, Radoslav Matej, Ann C. McKee, Catriona McLean, Ivan Milenkovic, Thomas J. Montine, Shigeo Murayama, Edward B. Lee, Jasmin Rahimi, Roberta D. Rodriguez, Annemieke Rozemüller, Julie A. Schneider, Christian Schultz, William Seeley, Danielle Seilhean, Colin Smith, Fabrizio Tagliavini, Masaki Takao, Dietmar Rudolf Thal, Jon B. Toledo, Markus Tolnay, Juan C. Troncoso, Harry V. Vinters, Serge Weis, Stephen B. Wharton, Charles L. White, Thomas Wisniewski, John M. Woulfe, Masahito Yamada, Dennis W. Dickson

Research output: Contribution to journal › Article › peer-review

354 Scopus citations

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.

Original language	English (US)
Pages (from-to)	87-102
Number of pages	16
Journal	Acta Neuropathologica
Volume	131
Issue number	1
DOIs	https://doi.org/10.1007/s00401-015-1509-x
State	Published - Jan 1 2016

Keywords

ARTAG
Aging
Tau
Tau astrogliopathy

ASJC Scopus subject areas

Pathology and Forensic Medicine
Clinical Neurology
Cellular and Molecular Neuroscience

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10.1007/s00401-015-1509-x

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Kovacs, G. G., Ferrer, I., Grinberg, L. T., Alafuzoff, I., Attems, J., Budka, H., Cairns, N. J., Crary, J. F., Duyckaerts, C., Ghetti, B., Halliday, G. M., Ironside, J. W., Love, S., Mackenzie, I. R., Munoz, D. G., Murray, M. E., Nelson, P. T., Takahashi, H., Trojanowski, J. Q., ... Dickson, D. W. (2016). Aging-related tau astrogliopathy (ARTAG): harmonized evaluation strategy. Acta Neuropathologica, 131(1), 87-102. https://doi.org/10.1007/s00401-015-1509-x

Kovacs, GG, Ferrer, I, Grinberg, LT, Alafuzoff, I, Attems, J, Budka, H, Cairns, NJ, Crary, JF, Duyckaerts, C, Ghetti, B, Halliday, GM, Ironside, JW, Love, S, Mackenzie, IR, Munoz, DG, Murray, ME, Nelson, PT, Takahashi, H, Trojanowski, JQ, Ansorge, O, Arzberger, T, Baborie, A, Beach, TG, Bieniek, KF, Bigio, EH, Bodi, I, Dugger, BN, Feany, M, Gelpi, E, Gentleman, SM, Giaccone, G, Hatanpaa, KJ, Heale, R, Hof, PR, Hofer, M, Hortobágyi, T, Jellinger, K, Jicha, GA, Ince, P, Kofler, J, Kövari, E, Kril, JJ, Mann, DM, Matej, R, McKee, AC, McLean, C, Milenkovic, I, Montine, TJ, Murayama, S, Lee, EB, Rahimi, J, Rodriguez, RD, Rozemüller, A, Schneider, JA, Schultz, C, Seeley, W, Seilhean, D, Smith, C, Tagliavini, F, Takao, M, Thal, DR, Toledo, JB, Tolnay, M, Troncoso, JC, Vinters, HV, Weis, S, Wharton, SB, White, CL, Wisniewski, T, Woulfe, JM, Yamada, M & Dickson, DW 2016, 'Aging-related tau astrogliopathy (ARTAG): harmonized evaluation strategy', Acta Neuropathologica, vol. 131, no. 1, pp. 87-102. https://doi.org/10.1007/s00401-015-1509-x

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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.",

keywords = "ARTAG, Aging, Tau, Tau astrogliopathy",

author = "Kovacs, {Gabor G.} and Isidro Ferrer and Grinberg, {Lea T.} and Irina Alafuzoff and Johannes Attems and Herbert Budka and Cairns, {Nigel J.} and Crary, {John F.} and Charles Duyckaerts and Bernardino Ghetti and Halliday, {Glenda M.} and Ironside, {James W.} and Seth Love and Mackenzie, {Ian R.} and Munoz, {David G.} and Murray, {Melissa E.} and Nelson, {Peter T.} and Hitoshi Takahashi and Trojanowski, {John Q.} and Olaf Ansorge and Thomas Arzberger and Atik Baborie and Beach, {Thomas G.} and Bieniek, {Kevin F.} and Bigio, {Eileen H.} and Istvan Bodi and Dugger, {Brittany N.} and Mel Feany and Ellen Gelpi and Gentleman, {Stephen M.} and Giorgio Giaccone and Hatanpaa, {Kimmo J.} and Richard Heale and Hof, {Patrick R.} and Monika Hofer and Tibor Hortob{\'a}gyi and Kurt Jellinger and Jicha, {Gregory A.} and Paul Ince and Julia Kofler and Enik{\"o} K{\"o}vari and Kril, {Jillian J.} and Mann, {David M.} and Radoslav Matej and McKee, {Ann C.} and Catriona McLean and Ivan Milenkovic and Montine, {Thomas J.} and Shigeo Murayama and Lee, {Edward B.} and Jasmin Rahimi and Rodriguez, {Roberta D.} and Annemieke Rozem{\"u}ller and Schneider, {Julie A.} and Christian Schultz and William Seeley and Danielle Seilhean and Colin Smith and Fabrizio Tagliavini and Masaki Takao and Thal, {Dietmar Rudolf} and Toledo, {Jon B.} and Markus Tolnay and Troncoso, {Juan C.} and Vinters, {Harry V.} and Serge Weis and Wharton, {Stephen B.} and White, {Charles L.} and Thomas Wisniewski and Woulfe, {John M.} and Masahito Yamada and Dickson, {Dennis W.}",

note = "Publisher Copyright: {\textcopyright} 2015, Springer-Verlag Berlin Heidelberg.",

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doi = "10.1007/s00401-015-1509-x",

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T1 - Aging-related tau astrogliopathy (ARTAG)

T2 - harmonized evaluation strategy

AU - Kovacs, Gabor G.

AU - Ferrer, Isidro

AU - Grinberg, Lea T.

AU - Alafuzoff, Irina

AU - Attems, Johannes

AU - Budka, Herbert

AU - Cairns, Nigel J.

AU - Crary, John F.

AU - Duyckaerts, Charles

AU - Ghetti, Bernardino

AU - Halliday, Glenda M.

AU - Ironside, James W.

AU - Love, Seth

AU - Mackenzie, Ian R.

AU - Munoz, David G.

AU - Murray, Melissa E.

AU - Nelson, Peter T.

AU - Takahashi, Hitoshi

AU - Trojanowski, John Q.

AU - Ansorge, Olaf

AU - Arzberger, Thomas

AU - Baborie, Atik

AU - Beach, Thomas G.

AU - Bieniek, Kevin F.

AU - Bigio, Eileen H.

AU - Bodi, Istvan

AU - Dugger, Brittany N.

AU - Feany, Mel

AU - Gelpi, Ellen

AU - Gentleman, Stephen M.

AU - Giaccone, Giorgio

AU - Hatanpaa, Kimmo J.

AU - Heale, Richard

AU - Hof, Patrick R.

AU - Hofer, Monika

AU - Hortobágyi, Tibor

AU - Jellinger, Kurt

AU - Jicha, Gregory A.

AU - Ince, Paul

AU - Kofler, Julia

AU - Kövari, Enikö

AU - Kril, Jillian J.

AU - Mann, David M.

AU - Matej, Radoslav

AU - McKee, Ann C.

AU - McLean, Catriona

AU - Milenkovic, Ivan

AU - Montine, Thomas J.

AU - Murayama, Shigeo

AU - Lee, Edward B.

AU - Rahimi, Jasmin

AU - Rodriguez, Roberta D.

AU - Rozemüller, Annemieke

AU - Schneider, Julie A.

AU - Schultz, Christian

AU - Seeley, William

AU - Seilhean, Danielle

AU - Smith, Colin

AU - Tagliavini, Fabrizio

AU - Takao, Masaki

AU - Thal, Dietmar Rudolf

AU - Toledo, Jon B.

AU - Tolnay, Markus

AU - Troncoso, Juan C.

AU - Vinters, Harry V.

AU - Weis, Serge

AU - Wharton, Stephen B.

AU - White, Charles L.

AU - Wisniewski, Thomas

AU - Woulfe, John M.

AU - Yamada, Masahito

AU - Dickson, Dennis W.

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N2 - 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.

AB - 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.

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KW - Aging

KW - Tau

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

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