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Safra Philanthropic Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003136","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Astrocytic tau pathology is a major feature of tauopathies and ageing\u2010related tau astrogliopathy (ARTAG). The substantia nigra (SN) is one of the important degenerative areas in tauopathies with parkinsonism. Nigral tau pathology is usually reported as neuronal predominant with less prominent astrocytic involvement. We aimed to identify cases with prominent astrocytic tau pathology in the SN.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We use the term nigral tau\u2010astrogliopathy (NITAG) to describe cases showing an unusually high density of ARTAG with less neuronal tau pathology in the SN. We collected clinical information and studied the distribution of tau pathology, morphological features and immunostaining profiles in three cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Three cases, all males with parkinsonism, were identified with the following clinicopathological diagnoses: (i) atypical parkinsonism with tau pathology reminiscent to that in postencephalitic parkinsonism (69\u2010year\u2010old); (ii) multiple system atrophy (73\u2010year\u2010old); (iii) traumatic encephalopathy syndrome\/chronic traumatic encephalopathy (84\u2010year\u2010old). Double\u2010labelling immunofluorescence confirmed co\u2010localization of GFAP and phosphorylated tau in affected astrocytes. Staining profiles of NITAG revealed immunopositivity for various phosphorylated tau antibodies. Some astrocytic tau lesions were also seen in other brainstem regions and cerebral grey matter.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We propose NITAG is a rare neuropathological feature, and not a distinct disease entity, in the frame of multiple system ARTAG, represented by abundant tau\u2010positive astrocytes in various brain regions but having the highest density in the SN. The concept of NITAG allows the stratification of cases with various background pathologies to understand its relevance and contribution to neuronal dysfunction.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nan.13000","type":"journal-article","created":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T09:26:05Z","timestamp":1721640365000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Ageing\u2010related tau astrogliopathy severely affecting the substantia nigra"],"prefix":"10.1111","volume":"50","author":[{"given":"Hidetomo","family":"Tanaka","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology and Tanz Centre for Research in Neurodegenerative Disease University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seojin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology and Tanz Centre for Research in Neurodegenerative Disease University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Martinez\u2010Valbuena","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology and Tanz Centre for Research in Neurodegenerative Disease University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blas","family":"Couto","sequence":"additional","affiliation":[{"name":"Edmond J. Safra Program in Parkinson's Disease, Rossy Program for PSP Research and the Morton and Gloria Shulman Movement Disorders Clinic Toronto Western Hospital  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Carmela","family":"Tartaglia","sequence":"additional","affiliation":[{"name":"University Health Network Memory Clinic Toronto Western Hospital  Toronto Ontario Canada"},{"name":"Department of Medicine\/Division of Neurology University of Toronto  Toronto Ontario Canada"},{"name":"Krembil Brain Institute Toronto Western Hospital  Toronto Ontario Canada"},{"name":"Canadian Concussion Centre, Krembil Brain Institute University Health Network  Toronto Ontario Canada"},{"name":"Tanz Centre for Research in Neurodegenerative Diseases University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier Sanchez\u2010Ruiz","family":"de Gordoa","sequence":"additional","affiliation":[{"name":"Department of Neurology Hospital Universitario de Navarra and Biobank, Navarrabiomed  Pamplona Navarra Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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