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.

Tau prions from Alzheimer’s disease and chronic traumatic encephalopathy patients propagate in cultured cells

“…Due to its greater sensitivity, only the Tau(4RD*LM)-YFP (2) cells were able to propagate the minor 4R component of the total aggregated tau, compared with the Tau(4RD*LM)-YFP(1) cells. One possible source of distinct 4R aggregates in these samples is aging-related tau astrogliopathy (ARTAG), which is selectively immunostained with 4R tau antibodies, even in PiD patients (55). Consistent with this finding, two PiD patient samples containing 4R tau astrocytic lesions infected the more sensitive Tau(4RD*LM)-YFP(2) cells.…”

Recent advances in neuropathology, biomarkers and therapeutic approach of multiple system atrophy

“…Repetitive falls due to MSA may also contribute to this pathology, but further investigation is necessary to support this hypothesis. Ageing-related tau astrogliopathy (ARTAG) is a term describing a morphological spectrum of tau-positive astroglial pathology mainly observed in elderly individuals 39. In the same series of MSA screened for CTE pathology, 10 (7%) had ARTAG 38.…”

Astrogliopathy in Tauopathies

“…Granular/fuzzy astrocytes are seen in the elderly and ARTAG [26,70], but also in other tauopathies such as in PSP [37]. Interestingly, tau-containing astrocytes are early lesions in PSP, CBD and FTLD-tau [28,[74][75][76].…”

“…Granular/fuzzy astrocytes are seen in the elderly and ARTAG [26,70], but also in other tauopathies such as in PSP [37].…”