Astrocytic tau pathologies in aged human brain

Argyrophilic and tau-positive abnormal structures in astrocytes are frequent in aged brains, with a new nomenclature of aging-related tau astrogliopathy (ARTAG) proposed. The two major cytomorphologies of ARTAG are thorn-shaped astrocytes (TSA) and granular or fuzzy tau immunoreactivity in processes of astrocytes (GFA). We selected 28 cases in which many AT8-identified astrocytic tauopathies were observed in the central nervous system from 330 routine aged autopsied cases, including Alzheimer's disease. AT8-identified and Gallyas silver staining-positive TSA were observed in subpial, subependymal, perivascular areas as well as white matter. These TSA were 4-repeat (4R) tau-positive. In contrast, 3-repeat (3R)-tau was negative in TSA, but positive in short thick cell processes, likely neuropil threads, in subpial and subependymal areas. The frequency of 3R-tau-positive processes was variable. Small dot-like AT8-identified astrocytic processes surrounding vessels in the neuropil were also positive for 4R-tau, but negative for 3R-tau. GFA in cerebral gray matter were AT8-identified and Gallyas-positive, and positive for 4R-tau but negative for 3R-tau. In this study, we did not identify 3R-tau+/4R-tau+ or 3R-tau+/4R-tau- astrocytes. Further studies are needed to clarify the nature and progression of glial tau-positive structures in ARTAG.