ARTAG in the basal forebrain: Widening the constellation of astrocytic tau pathology

Tauopathies are disorders characterised by the abnormal accumulation of hyperphosphorylated tau protein within neurons and glial cells. Alzheimer’s disease (AD), the most common form of tauopathy, features a stereotypical, staged progression of neurofibrillary tangle (NFT) and neuritic tau pathology through the brain [1]. However, age-related NFT and neuritic tau pathologies have also commonly been identified in cognitively normal and ‘tangle-only dementia’ cases in the absence of amyloid-β peptide (Aβ) pathology. This has now been given the term ‘primary age-related tauopathy’ (PART) to distinguish it from AD [3]. Furthermore, astroglial tau aggregations have been increasingly recognised to be present within the aging brain independently of any co-existing neuropathological disorders or cognitive impairment. This unique astroglial tau pathology has been termed aging-related tau astrogliopathy (ARTAG) [6]. ARTAG exists in two distinct morphological forms as thorn-shaped astrocytes (TSA) and granular/fuzzy astrocytes (GFA). In addition, these tau immunoreactive astrocytes show a unique distribution within the brain, with TSA and/or GFA commonly found in subpial, subependymal and perivascular locations, as well as in clusters within the white and grey matter.