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We previously identified distinct microglial signatures that were enriched in AD donors and associated with amyloid and tau, respectively. Here we generated a snRNAseq dataset from postmortem control and AD cases and analyzed alterations in cell\u2013cell communication pathways that might be relevant to AD pathophysiology. One signaling pathway perturbed in AD cases involved\n                    <jats:italic>SPP1<\/jats:italic>\n                    , and while this pathway was also present in control samples, microglia\u2013microglia SPP1 signaling was restricted to AD donors. Further analyses within microglia\u2013microglia signaling predict AD\u2010specific induction of\n                    <jats:italic>GAS6\u2010AXL<\/jats:italic>\n                    signaling (from inflammatory and ribosomal microglia), and\n                    <jats:italic>SPP1\u2010ITGAV\/ITGB5<\/jats:italic>\n                    signaling (from disease\u2010associated and inflammatory microglia, among others). Together, these findings might in part explain the increased microglia phagocytic profile described in AD. RNAscope confirmed enrichment of\n                    <jats:italic>SPP1<\/jats:italic>\n                    expressing microglia near amyloid plaques in AD brain tissue samples. These data indicate altered cellular communications between microglia in the AD brain.\n                  <\/jats:p>","DOI":"10.1002\/glia.70210","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T05:25:43Z","timestamp":1785907543000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Predicting Relevant Microglia\u2010Associated Cell\u2013Cell Communication Pathways in Alzheimer's Disease: A Role for\n                    <scp>SPP1<\/scp>"],"prefix":"10.1002","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3005-730X","authenticated-orcid":false,"given":"Janssen M.","family":"Kotah","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences University of Groningen, University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3687-6210","authenticated-orcid":false,"given":"Marina Trombetta","family":"Lima","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences University of Groningen, University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1321-6412","authenticated-orcid":false,"given":"Esm\u00e9e C.","family":"Dragt","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences University of Groningen, University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4784-108X","authenticated-orcid":false,"given":"Asimenia","family":"Voulgaroglou","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences University of Groningen, University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nieske","family":"Brouwer","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences University of Groningen, University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9752-4756","authenticated-orcid":false,"given":"Inge R.","family":"Holtman","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences University of Groningen, University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0211-8283","authenticated-orcid":false,"given":"Susanne M.","family":"Kooistra","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences University of Groningen, University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8941-0353","authenticated-orcid":false,"given":"Bart J. 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