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Tau is a target of therapy and the strategy includes either the elimination of pathological tau aggregates or reducing\n                    <jats:italic>MAPT<\/jats:italic>\n                    expression, and thus the amount of tau protein made to prevent its aggregation. Disease-associated tau affects brain regions in a sequential manner that includes cell-to-cell spreading. Involvement of glial cells that show tau aggregates is interpreted as glial cells taking up misfolded tau assuming that glial cells do not express enough\n                    <jats:italic>MAPT<\/jats:italic>\n                    . Although studies have evaluated\n                    <jats:italic>MAPT<\/jats:italic>\n                    expression in human brain tissue homogenates, it is not clear whether\n                    <jats:italic>MAPT<\/jats:italic>\n                    expression is compromised in cells accumulating pathological tau. To address these perplexing aspects of disease pathogenesis, this study used RNAscope combined with immunofluorescence (AT8), and single-nuclear(sn) RNAseq to systematically map and quantify\n                    <jats:italic>MAPT<\/jats:italic>\n                    \u00a0expression dynamics across different cell types and brain regions in controls (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20093) and evaluated whether tau cytopathology affects\n                    <jats:italic>MAPT<\/jats:italic>\n                    expression in PSP (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20093).\n                    <jats:italic>MAPT<\/jats:italic>\n                    \u00a0transcripts were detected in neurons, astrocytes and oligodendrocytes, and varied between brain regions\u00a0and within each cell type, and were preserved in all cell types with tau aggregates in PSP. These results propose a complex scenario in all cell types, where, in addition to the ingested misfolded tau, the preserved cellular\n                    <jats:italic>MAPT<\/jats:italic>\n                    expression provides a pool for local protein production that can (1) be phosphorylated and aggregated, or (2) feed the seeding of ingested misfolded tau by providing physiological tau, both accentuating the pathological process. Since\u00a0tau cytopathology does not compromise\n                    <jats:italic>MAPT<\/jats:italic>\n                    gene expression in PSP, a complete loss of tau protein expression as an early pathogenic component is less likely. These observations provide rationale for a dual approach to therapy by decreasing cellular\n                    <jats:italic>MAPT<\/jats:italic>\n                    expression and targeting removal of misfolded tau.\n                  <\/jats:p>","DOI":"10.1007\/s00401-023-02604-x","type":"journal-article","created":{"date-parts":[[2023,6,24]],"date-time":"2023-06-24T09:00:21Z","timestamp":1687597221000},"page":"395-414","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Cell-specific MAPT gene expression is preserved in neuronal and glial tau cytopathologies in progressive supranuclear palsy"],"prefix":"10.1007","volume":"146","author":[{"given":"Shelley L.","family":"Forrest","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seojin","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasna","family":"Nassir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Martinez-Valbuena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Sackmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Awab","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Carmela","family":"Tartaglia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars M.","family":"Ittner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony E.","family":"Lang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Uddin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3841-5511","authenticated-orcid":false,"given":"Gabor G.","family":"Kovacs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,6,24]]},"reference":[{"key":"2604_CR1","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1007\/s00401-013-1171-0","volume":"126","author":"Z Ahmed","year":"2013","unstructured":"Ahmed Z, Bigio EH, Budka H, Dickson DW, Ferrer I, Ghetti B et al (2013) Globular glial tauopathies (GGT): consensus recommendations. 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Fox Foundation, the Ontario Brain Institute, Parkinson Foundation, Parkinson Canada, and W. Garfield Weston Foundation; is serving as an expert witness in litigation related to paraquat and Parkinson\u2019s disease, received publishing royalties from Elsevier, Saunders, Wiley-Blackwell, Johns Hopkins Press, and Cambridge University Press. GGK is member of the Acta Neuropathologica Editorial Board but was not involved in the editorial handling of this article. GGK has served as an advisor for Biogen; received royalty for 5G4 synuclein antibody and publishing royalties from Wiley, Cambridge University Press and Elsevier, received grants from Edmond J Safra Philanthropic Foundation, Rossy Foundation, Michael J. Fox Foundation, Parkinson Canada, Canada, Canada Foundation for Innovation, MSA\u00a0Coalition, and National Institutes of Health (NIH). 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