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Microglia engulf pathological proteins, but how they endocytose tau is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We measured endocytosis of different tau species by microglia after pharmacological modulation of macropinocytosis or clathrin\u2010mediated endocytosis (CME) or antagonism\/genetic depletion of known tau receptors heparan\u2010sulfate proteoglycans (HSPGs) and low\u2010density lipoprotein receptor\u2010related protein 1 (LRP1).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Dynamin inhibition decreased microglial endocytosis of all tested tau species. Meanwhile, HSPG antagonism blocked only fibril uptake, and LRP1 antagonism or genetic depletion inconsistently inhibited the endocytosis of fibrils and monomers. Cre recombinase robustly enhanced tau uptake with partial selectivity for fibrils.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These data show that microglia take up both tau monomers and aggregates via a dynamin\u2010dependent form of endocytosis (eg, CME) but may differ in using HSPGs for entry depending on species.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Microglial endocytosis of tau monomers and fibrils is dynamin\u2010dependent.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>HSPG antagonism blocks microglial uptake of tau fibrils but not monomers.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>LRP1 antagonism or knockdown inconsistently inhibits tau uptake.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>TAT\u2010Cre stimulates semi\u2010selective uptake of fibrils over monomers.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.14418","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T06:05:10Z","timestamp":1734933910000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Microglia internalize tau monomers and fibrils using distinct receptors but similar mechanisms"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4152-4583","authenticated-orcid":false,"given":"Kristian F.","family":"Falkon","sequence":"first","affiliation":[{"name":"Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases University of Texas Health Science Center San Antonio San Antonio Texas USA"},{"name":"Department of Pharmacology University of Texas Health Science Center San Antonio San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Danford","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Texas Health Science Center San Antonio San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Gutierrez Kuri","sequence":"additional","affiliation":[{"name":"Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases University of Texas Health Science Center San Antonio San 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