Multisite Assessment of Aging-Related Tau Astrogliopathy (ARTAG)

Abstract

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.

Non-Alzheimer’s contributions to dementia and cognitive resilience in The 90+ Study

“…The occurrence of incidental α-synuclein-positive Lewy bodies and Lewy neurites is increasingly being reported [7, 15, 27, 33, 35] and the 17% prevalence in The 90+ Study is in line with other cohorts without overt parkinsonism. Intriguingly, Lewy pathology was associated with dementia even though there was a weak correlation between the clinical diagnosis of Lewy body disease and Lewy pathology: 12 cases were diagnosed with LBD or AD/LBD, of which only 4 had Lewy pathology.…”

“…ARTAG was also common in this cohort and, to our knowledge, this is the first study to show an association of ARTAG with clinical dementia in a large cohort of elderly individuals [27, 28, 43, 46]. While the importance of CVD and HS is increasingly recognized [20], ARTAG’s clinical relevance has only been suggested in a small cohort of individuals [25].…”

“…Aging can also result in the accumulation of non-AD pathologies, including proteinopathies such as α-synuclein-positive Lewy bodies, TDP-43-positive inclusions and aging-related tau astrogliopathy (ARTAG), as well as cerebrovascular disease (CVD) and hippocampal sclerosis (HS) [15, 27, 33, 35]. Incidental Lewy bodies are generally absent in those under 60 years, but are found in 17–25% of aged brains without parkinsonism and clinical dementia.…”

“…ARTAG also rises in frequency with increasing age [23]. While rare under age 60 years, ARTAG has been found in almost half of brains over age 75 years [24, 26, 27]. ARTAG occurs as different types in multiple anatomical areas.…”

Astrocytic tau pathologies in aged human brain

“…Recently, argyrophilic and tau‐positive abnormal structures in astrocytes were frequently noted in aged brains, with the new nomenclature of ARTAG proposed . Reports on tau astrogliopathies are increasing . Ferrer et al , found that tau pathology in glial cells largely parallels, but is not identical to, that in neurons in many tauopathies .…”