{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:46:28Z","timestamp":1791895588428,"version":"4.3.4"},"reference-count":56,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:00:00Z","timestamp":1791590400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Microglia drive neuroinflammation in Alzheimer's disease (AD), yet no approved therapy targets this compartment. Human genome-wide association studies consistently implicate innate immune loci in AD risk, establishing microglial transcriptional programs as therapeutically relevant but pharmacologically underexploited targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We sought to identify transcription factors (TFs) governing microglial state transitions computationally and to nominate structurally tractable drug repurposing candidates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We applied trajectory inference (PAGA), pseudobulk DESeq2, pySCENIC gene regulatory network (GRN) inference, CellChat, and virtual screening of 1962 approved compounds to 236,002 microglial nuclei from 84 donors (SEA-AD atlas).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">IKZF1<\/jats:italic>\n                      was the sole target TF retained under cisTarget v10 motif constraints, with peak regulon activity in LateAD-DAM (pseudotime \u03c1\u2009=\u2009+\u20090.309) and replication in an independent bulk cohort (GSE95587; adjusted p\u2009=\u20090.004). CellChat identified SLIT2\u2192ROBO2 from multiple neuron subtypes (predominantly inhibitory interneurons) as the top predicted pathway to microglia. Tafamidis (\u2192IRF8) and diflunisal (\u2192PPARG) were top virtual screening hits; all evaluated compounds failed the pre-specified selectivity threshold.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">IKZF1<\/jats:italic>\n                      is prioritized as a candidate late-disease microglial TF, supported by six convergent evidence dimensions including independent bulk replication. Tafamidis and diflunisal are low-confidence repurposing hypotheses requiring experimental validation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261496918","type":"journal-article","created":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T12:22:19Z","timestamp":1791634939000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Single-cell gene networks nominate\n                    <i>IKZF1<\/i>\n                    as an Alzheimer's disease microglial regulator"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9641-6745","authenticated-orcid":false,"given":"\u00c7a\u011fr\u0131","family":"\u00d6zkurt","sequence":"first","affiliation":[{"name":"Hacettepe University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,10,10]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(25)01389-3"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.018"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.08.037"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1195-2"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2012.02.014"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-021-00199-0"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2018.04.008"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4463"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/gm340"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-024-01774-5"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1663-x"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3599"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn1805"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.70078"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2022.105684"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21246-9"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad1011"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03819-2"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1005659"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpcb.3c06662"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1021\/cn100008c"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.5c02271"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.1c00645"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3845"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05688-9"},{"key":"e_1_3_3_27_2","doi-asserted-by":"crossref","unstructured":"McInnes L Healy J Melville J. 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