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To investigate if the three p-tau variants are found to the same degree in different tau structures and if their co-localization is affected by the diagnosis and presence of A\u00df plaques, we immunostained sections of the entorhinal cortex (EC) and inferior temporal gyrus (ITG) from non-demented controls (NC), patients with Alzheimer\u2019s disease (AD), and primary age-related tauopathy (PART) against p-tau217, p-tau231, and p-tau205 together with Methoxi-X04. An analysis using confocal microscopy showed that the co-localization variable, the Pearson correlation coefficient (PCC), was significantly higher between p-tau231 and p-tau205 in neurofibrillary tangles compared to neuropil threads and dystrophic neurites in plaques. The PCC value between all three p-tau variants in the neuropil threads was significantly lower in the ECs of patients with AD compared to the NC and in the ITGs of patients with AD, with a high A\u00df load compared to PART. The lowered value was associated with proportionally higher amounts of non-colocalized p-tau231 and p-tau217 compared to p-tau205, and the PCC values were negatively correlated with A\u00df and the tangle loads in patients with AD, but positively correlated with tangles in PART. These results suggest that the proportion of and co-localization between p-tau217, p-tau231, and p-tau205 are dependent on cellular localization and are altered in response to AD pathology in a spatial\u2013temporal manner.<\/jats:p>","DOI":"10.3390\/cells13040331","type":"journal-article","created":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T04:47:45Z","timestamp":1707713265000},"page":"331","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The Relationship between p-tau217, p-tau231, and p-tau205 in the Human Brain Is Affected by the Cellular Environment and Alzheimer\u2019s Disease Pathology"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9957-1801","authenticated-orcid":false,"given":"Malin","family":"Wennstr\u00f6m","sequence":"first","affiliation":[{"name":"Cognitive Disorder Research Unit, Department of Clinical Sciences Malm\u00f6, Lund University, 21428 Malm\u00f6, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8202-6455","authenticated-orcid":false,"given":"Nina","family":"Schultz","sequence":"additional","affiliation":[{"name":"Cognitive Disorder Research Unit, Department of Clinical Sciences Malm\u00f6, Lund University, 21428 Malm\u00f6, Sweden"},{"name":"Clinical Memory Research Unit, Department of Clinical Sciences Malm\u00f6, Lund University, 21146 Malm\u00f6, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6715-0210","authenticated-orcid":false,"given":"Paula Mille","family":"Gallardo","sequence":"additional","affiliation":[{"name":"Cognitive Disorder Research Unit, Department of Clinical Sciences Malm\u00f6, Lund University, 21428 Malm\u00f6, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The Netherlands Brain Bank","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geidy E.","family":"Serrano","sequence":"additional","affiliation":[{"name":"Banner Sun Health Research Institute, Sun City, AZ 85351, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas G.","family":"Beach","sequence":"additional","affiliation":[{"name":"Banner Sun Health Research Institute, Sun City, AZ 85351, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suchira","family":"Bose","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Arlington Square West, Bracknell RG12 1PU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oskar","family":"Hansson","sequence":"additional","affiliation":[{"name":"Clinical Memory Research Unit, Department of Clinical Sciences Malm\u00f6, Lund University, 21146 Malm\u00f6, Sweden"},{"name":"Memory Clinic, Sk\u00e5ne University Hospital, 20205 Malm\u00f6, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13024-019-0333-5","article-title":"The neuropathological diagnosis of Alzheimer\u2019s disease","volume":"14","author":"DeTure","year":"2019","journal-title":"Mol. 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