Understanding the Relevance of Aging-Related Tau Astrogliopathy (ARTAG)

Gabor Kovacs

doi:10.3390/neuroglia1020023

Abstract

Aging-related tau astrogliopathy (ARTAG) is an umbrella term that encompasses a spectrum of morphological abnormalities seen in astrocytes of the aging brain using immunostaining for pathological forms of the microtubule-associated protein tau. Morphologies of ARTAG include thorn-shaped astrocytes (TSA), and additionally granular/fuzzy astrocytes (GFA) characterized by fine granular tau immunoreactivity extending into the astrocytic processes. Thorn-shaped astrocytes can be present in the same brain in subpial, subependymal, perivascular, and white and gray matter locations together with GFAs, which are seen in the gray matter. Primary tauopathies show ARTAG-related morphologies as well, moreover, GFA has been proposed to present a conceptual link between brain ageing and primary tauopathies. Sequential distribution patterns have been recognized for subpial, white and gray matter ARTAG. This either suggests the involvement of astrocytes in the propagation of tau pathology or reflects the consequence of a long-term pathogenic process such as barrier dysfunction, local mechanical impact, or early response to neuronal degeneration. The concept of ARTAG facilitated communication among neuropathologists and researchers, informed biomarker researchers with focus on tau-related indicators and motivated further exploration of the significance of astrocytic lesions in various neurodegenerative conditions.

Highlights

Aging-related tau astrogliopathy (ARTAG) is an umbrella term that encompasses a spectrum of morphological abnormalities seen in astrocytes using immunostaining for pathological forms of the microtubule-associated protein tau, mainly in the aging brain [1]
ARTAG includes morphologies described originally as thorn-shaped astrocytes (TSA) as well as fine granular tau immunoreactivity extending into the astrocytic processes in the gray matter, called granular/fuzzy astrocytes (GFA) [1]
Since GFA-like morphologies are seen in primary tauopathies, we introduced the concept that, analogously to the pretangles, which might be a preceding form of neurofibrillary tangles, the first step of astrocytic pathology might be the fine granular accumulation in astrocytic processes [14,20]

Summary

Introduction

Aging-related tau astrogliopathy (ARTAG) is an umbrella term that encompasses a spectrum of morphological abnormalities seen in astrocytes using immunostaining for pathological forms of the microtubule-associated protein tau, mainly in the aging brain [1]. ARTAG includes morphologies described originally as thorn-shaped astrocytes (TSA) as well as fine granular tau immunoreactivity extending into the astrocytic processes in the gray matter, called granular/fuzzy astrocytes (GFA) [1]. Ikeda and colleagues were the first to describe TSAs in the subpial or subependymal regions of the gray and white matter, and frequently in the depths of the gyri, as well as in the basal forebrain and brainstem, in aged individuals [2,3,4] This was followed by a study from Schultz et al reporting a high prevalence of TSAs in the aged human medial temporal lobe, at the level of the amygdala [5].

ARTAG and Primary Tauopathies

ARTAG and Various Disorders Including Chronic Traumatic Encephalopathy

Sequential Distribution of ARTAG

What Is the Clinical Relevance of ARTAG?

Findings

Perspectives