Ageing-related tau astrogliopathy in a population-based study of the oldest old (Vantaa 85+)

Ageing-related tau astrogliopathy (ARTAG) is a common tau pathology affecting astrocytes, frequently seen in the aged brain. However, comprehensive studies on ARTAG in a population-/community-based setting are still scarce and its significance needs further clarification. We assessed ARTAG changes (thorn-shaped and granular/fuzzy astrocytes) in 304 neuropathologically examined individuals of the population-based Vantaa 85+ study by tau immunohistochemistry (AT8 antibody). We analysed laminar subpial, subependymal, perivascular, white and grey matter ARTAG changes in various locations of the medial temporal lobe, neocortex, subcortical structures and midbrain. ARTAG was a frequent finding, present in 79.6% of individuals. In accordance with previous studies, we could confirm the association of different ARTAG subtypes with male sex. We also found significant associations between ARTAG subtypes and several co-pathologies, most notably limbic-predominant age-related TDP-43 encephalopathy-neuropathological changes, hippocampal sclerosis of ageing, argyrophilic grains and cerebrovascular disease (cortical microinfarcts and small brain infarcts in various locations). Additionally, we evaluated the presence of previously described specific anatomical gliopathies, such as those seen in the mammillary bodies and substantia nigra (nigral tau-astrogliopathy). This comprehensive study provides valuable information on ARTAG frequency in the oldest-old, and on its interplay with other brain pathologies.