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We recently observed significantly increased hippocampal tau pathology in rats injected with pseudophosphorylated human tau (2N4R tau\n                    <jats:sup>T175D<\/jats:sup>\n                    ) co\u2010expressing an ALS\u2010associated TAR DNA\u2010binding protein 43 (TDP\u201043) mutant (TDP\u201043\n                    <jats:sup>M337V<\/jats:sup>\n                    ) when compared to wild\u2010type rats. To understand this mechanism, we examined whether the extracellular vesicles (EVs) derived from wild\u2010type TDP\u201043 (wtTDP\u201043) or tau\u2010expressing cells could transfer expression of these proteins to recipient cells, and whether co\u2010localization of these proteins occurs. mCherry\u2010\n                    <jats:italic>wt<\/jats:italic>\n                    TDP\u201043 or EGFP\u2010tau constructs were expressed in HEK293 or SH\u2010SY5Y cells. The secretome and EV fractions contained\n                    <jats:italic>wt<\/jats:italic>\n                    TDP\u201043 or 2N4R tau protein and RNA, and could transfer proteins into nontransfected cells. Co\u2010localization was also detected in the cytosol of recipient cells.\n                    <jats:italic>In silico<\/jats:italic>\n                    modeling of tau and TDP\u201043 interactions suggests hydrogen bonding underlies this interaction. These studies further our understanding of the interaction between tau and TDP\u201043 by demonstrating their ability to co\u2010aggregate and in providing a mechanism by which cell\u2013cell transfer of either protein via extracellular vesicles can lead to these synergistic interactions.\n                  <\/jats:p>","DOI":"10.1111\/febs.70336","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T07:12:13Z","timestamp":1763449933000},"page":"1495-1515","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Co\u2010localization of tau and\n                    <scp>TDP<\/scp>\n                    \u201043 after extracellular vesicle delivery to cells"],"prefix":"10.1111","volume":"293","author":[{"given":"Farhang","family":"Aliakbari","sequence":"first","affiliation":[{"name":"Molecular Medicine, Robarts Research Institute, Schulich School of Medicine and Dentistry Western University  London Canada"},{"name":"Department of Bioprocess Engineering National Institute of Genetic Engineering and Biotechnology  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Volkening","sequence":"additional","affiliation":[{"name":"Molecular Medicine, Robarts Research Institute, Schulich School of Medicine and Dentistry Western University  London Canada"},{"name":"Clinical Neurological Sciences, Schulich School of Medicine and Dentistry Western University  London Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahra","family":"Nayeri","sequence":"additional","affiliation":[{"name":"Department of Bioprocess Engineering National Institute of Genetic Engineering and Biotechnology  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aysegul Yucel","family":"Polat","sequence":"additional","affiliation":[{"name":"Molecular Medicine, Robarts Research Institute, Schulich School of Medicine and Dentistry Western University  London Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Donison","sequence":"additional","affiliation":[{"name":"Molecular Medicine, Robarts Research Institute, Schulich School of Medicine and Dentistry Western University  London Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Palik","sequence":"additional","affiliation":[{"name":"Molecular Medicine, Robarts Research Institute, Schulich School of Medicine and Dentistry Western University  London Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1988-6262","authenticated-orcid":false,"given":"Michael J.","family":"Strong","sequence":"additional","affiliation":[{"name":"Molecular Medicine, Robarts Research Institute, Schulich School of Medicine and Dentistry Western University  London Canada"},{"name":"Clinical Neurological Sciences, Schulich School of Medicine and Dentistry Western University  London Canada"},{"name":"Department of Pathology and Laboratory Medicine, Schulich School of Medicine and Dentistry Western University  London Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1134108"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70090-5"},{"key":"e_1_2_10_4_1","doi-asserted-by":"crossref","unstructured":"Report A. s. 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