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Microglia and astrocytes have been described as playing important roles in synaptic spreading of toxic tau in several neurodegenerative diseases (NDs). Here, we have investigated the immunological and biochemical properties of aggregated tau species in different brain cell types in tau\u2010induced neurodegenerative diseases such as Alzheimer's disease (AD), progressive supranuclear palsy (PSP), and dementia with Lewy bodies (DLB). Additionally, we examined nuclear size, nuclear density, and chromatin compaction in neuronal and glial cells from diseased brain tissues. Microscopic\u2010histological examination was performed using in\u2010house mouse monoclonal antibodies for <jats:italic>t<\/jats:italic>oxic <jats:italic>t<\/jats:italic>au <jats:italic>c<\/jats:italic>onformers (TTC\u2010M1 and TTC\u2010M2) and <jats:italic>t<\/jats:italic>au <jats:italic>o<\/jats:italic>ligomers (TOMA1\u20104). By immunohistochemistry and co\u2010immunofluorescence assays using TOMA\/TTC\u2010Ms and cell\u2010type specific markers for neurons, astrocytes, and microglia, we observed that TOMA\/TTC\u2010Ms were immunoreactive to diverse tau species in different cell types. Analysis of colocalization coefficients indicated an increased pathological tau deposition mainly in the neurons. Western blot analysis of brain homogenates using TOMA\/TTC\u2010Ms revealed distinct patterns of tau aggregation in each disease, suggesting that TOMA\/TTC\u2010Ms can distinguish between different tau aggregates present in different tauopathies. Additionally, using DAPI staining, we observed that neuronal and astrocytic nuclei had significantly greater nuclear area and increased chromatin compaction in AD cortices compared to non\u2010demented controls. In contrast, reduction in nuclear density\/area and more relaxed chromatin was noticed in DLB neurons, astrocytes and microglia and PSP astrocytes and microglia. Cell\u2010type specific tropism of toxic tau species in tauopathies will provide a greater understanding of the involvement of different brain cell types in tau pathology. In this study, we observed that each disease presented cell\u2010type specific nuclear phenotype and tau deposition pattern.<\/jats:p>","DOI":"10.1111\/bpa.13112","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T07:45:26Z","timestamp":1661327126000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Pathological tau signatures and nuclear alterations in neurons, astrocytes and microglia in Alzheimer's disease, progressive supranuclear palsy, and dementia with Lewy bodies"],"prefix":"10.1111","volume":"33","author":[{"given":"Mauro","family":"Montalbano","sequence":"first","affiliation":[{"name":"Mitchell Center for Neurodegenerative Disorders University of Texas Medical Branch, UTMB  Galveston Texas USA"},{"name":"Department of Neurology University of Texas Medical Branch, UTMB  Galveston Texas 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