Association of glial tau pathology and LATE-NC in the ageing brain

Ageing-related pathologies of the brain include neurofibrillary tangles, argyrophilic grains, ageing-related tau astrogliopathy (ARTAG), limbic-predominant age-related TDP-43 encephalopathy-neuropathological change (LATE-NC), vascular pathology and corpora amylacea. This study used an unbiased approach to evaluate a broad range of pathologies in an unselected European community-dwelling ageing cohort of 101 individuals (77-90 years). Pathological alterations observed included neurofibrillary tangles and corpora amylacea in all cases, ARTAG (79%), Thal amyloid-β phase >1 (60%), cerebral amyloid angiopathy (39%), Lewy bodies (22%), LATE-NC (21%), oligodendroglial tau-positive coiled bodies (33%), and argyrophilic grains (15%). We demonstrate association of LATE-NC with the previously unappreciated age-related tau oligodendrogliopathy (ARTOG) and highlight the association of LATE-NC with various ARTAG types pointing toward common pathogenic aspects. Only neurofibrillary tangles and LATE-NC were associated with cognitive decline. This study broadens the spectrum of age-related brain pathologies and highlights a novel ageing-related tau pathology in oligodendroglia. Results from this study suggest overlapping pathogenic mechanisms between LATE-NC and glial tau pathologies in the medial temporal lobe.