Aging-related tau astrogliopathy (ARTAG): harmonized evaluation strategy
2016 (English)In: Acta Neuropathologica, ISSN 0001-6322, E-ISSN 1432-0533, Vol. 131, no 1, 87-102 p.Article in journal (Refereed) PublishedText
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.
Place, publisher, year, edition, pages
2016. Vol. 131, no 1, 87-102 p.
Aging, ARTAG, Tau astrogliopathy, Tau
IdentifiersURN: urn:nbn:se:uu:diva-275556DOI: 10.1007/s00401-015-1509-xISI: 000367601800006PubMedID: 26659578OAI: oai:DiVA.org:uu-275556DiVA: diva2:900498
FunderEU, FP7, Seventh Framework Programme, 278486NIH (National Institute of Health), P30 AG10133NIH (National Institute of Health), R01 AG040311NIH (National Institute of Health), P01 AG019724-03NIH (National Institute of Health), P50 AG023501NIH (National Institute of Health), P50 AG016574NIH (National Institute of Health), P50 NS072187NIH (National Institute of Health), AG010124NIH (National Institute of Health), AG017586NIH (National Institute of Health), P50 AG005138NIH (National Institute of Health), AG028383NIH (National Institute of Health), P30AG12300