{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:29:17Z","timestamp":1791944957195,"version":"4.3.4"},"reference-count":107,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Microglia have been implicated in the templated spread of tau aggregates in tauopathies through mouse studies. However, it is unclear whether these findings translate to human disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We challenged human induced pluripotent stem cell (iPSC)\u2010derived microglia\u2010like\u2010cells\u00a0(iMGL) with monomeric and fibrillar recombinant tau and tau purified from Alzheimer's patient brains, examining in detail the uptake, processing, release, and seeding of tau by microglia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>iMGL take up tau via lipoprotein receptor\u2010related protein 1 (LRP)1 and heparan sulfate proteoglycans, with leucine\u2010rich repeat kinase 2 affecting LRP1 trafficking. Monomeric tau is digested effectively with minimal effects on iMGL, but recombinant or brain\u2010derived tau fibrils induce chemokine\/interferon response subtypes, alongside downregulation of homeostatic genes. Fibrillar tau is degradation\u2010resistant, can escape into the cytoplasm, and becomes phosphorylated on two specific residues. iMGL release partially digested fibrillar tau, including in extracellular vesicles, visualized by cryo\u2010electron microscopy, that seed aggregation in neurons.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Our study reveals new insights into human microglial responses to tau, highlighting opportunities to limit pathogenic tau spread.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71337","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T05:57:02Z","timestamp":1775541422000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Tracking tau and cellular responses in human iPSC\u2010microglia: from uptake to seedable secretion, including in extracellular vesicles"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1742-0151","authenticated-orcid":false,"given":"Maria Kreger","family":"Karabova","sequence":"first","affiliation":[{"name":"James and Lillian Martin Centre for Stem Cell Research, Sir William Dunn School of Pathology University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"del Ser\u2010Badia","sequence":"additional","affiliation":[{"name":"James and Lillian Martin Centre for Stem Cell Research, Sir William Dunn School of Pathology University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Hedegaard","sequence":"additional","affiliation":[{"name":"James and Lillian Martin Centre for Stem Cell Research, Sir William Dunn School of Pathology University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam J.","family":"Washer","sequence":"additional","affiliation":[{"name":"James and Lillian Martin Centre for Stem Cell Research, Sir William Dunn School of Pathology University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeynep","family":"Baykam","sequence":"additional","affiliation":[{"name":"James and Lillian Martin Centre for Stem Cell Research, Sir William Dunn School of Pathology University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darragh P.","family":"O'Brien","sequence":"additional","affiliation":[{"name":"Target Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iolanda","family":"Vendrell","sequence":"additional","affiliation":[{"name":"Target Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svenja S.","family":"Hester","sequence":"additional","affiliation":[{"name":"Target Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Fischer","sequence":"additional","affiliation":[{"name":"Target Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Errin","family":"Johnson","sequence":"additional","affiliation":[{"name":"Sir William Dunn School of Pathology University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte E.","family":"Melia","sequence":"additional","affiliation":[{"name":"Sir William Dunn School of Pathology University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teige R. 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