{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T18:31:44Z","timestamp":1789497104151,"version":"build-2803163510"},"reference-count":113,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T00:00:00Z","timestamp":1733443200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG076448"],"award-info":[{"award-number":["R01AG076448"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG084250"],"award-info":[{"award-number":["R01AG084250"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["U01AG073323"],"award-info":[{"award-number":["U01AG073323"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG066707"],"award-info":[{"award-number":["R01AG066707"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG082118"],"award-info":[{"award-number":["R01AG082118"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["RF1AG082211"],"award-info":[{"award-number":["RF1AG082211"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R56AG074001"],"award-info":[{"award-number":["R56AG074001"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R21AG083003"],"award-info":[{"award-number":["R21AG083003"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG053798"],"award-info":[{"award-number":["R01AG053798"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R35AG071476"],"award-info":[{"award-number":["R35AG071476"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20GM109025"],"award-info":[{"award-number":["P20GM109025"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["RF1NS133812"],"award-info":[{"award-number":["RF1NS133812"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["U01NS093334"],"award-info":[{"award-number":["U01NS093334"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>High microglial heterogeneities hinder the development of microglia\u2010targeted treatment for Alzheimer's disease (AD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We integrated 0.7 million single\u2010nuclei RNA\u2010sequencing transcriptomes from human brains using a variational autoencoder. We predicted AD\u2010relevant microglial subtype\u2010specific transition networks for disease\u2010associated microglia (DAM), tau microglia, and neuroinflammation\u2010like microglia (NIM). We prioritized drugs by specifically targeting microglia\u2010specific transition networks and validated drugs using two independent real\u2010world patient databases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      We identified putative AD molecular drivers (e.g.,\n                      <jats:italic>SYK<\/jats:italic>\n                      ,\n                      <jats:italic>CTSB<\/jats:italic>\n                      , and\n                      <jats:italic>INPP5D<\/jats:italic>\n                      ) in transition networks of DAM and NIM. Via specifically targeting NIM, we identified that usage of ketorolac was associated with reduced AD incidence in both MarketScan (hazard ratio [HR]\u00a0=\u00a00.89) and INSIGHT (HR\u00a0=\u00a00.83) Clinical Research Network databases, mechanistically supported by ketorolac\u2010treated transcriptomic data from AD patient induced pluripotent stem cell\u2013derived microglia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>This study offers insights into the pathobiology of AD\u2010relevant microglial subtypes and identifies ketorolac as a potential anti\u2010inflammatory treatment for AD.<\/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>An integrative analysis of\u00a0\u2248 0.7 million single\u2010nuclei RNA\u2010sequencing transcriptomes from human brains identified Alzheimer's disease (AD)\u2013relevant microglia subtypes.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Network\u2010based analysis identified putative molecular drivers (e.g.,\n                            <jats:italic>SYK, CTSB, INPP5D<\/jats:italic>\n                            ) of transition networks between disease\u2010associated microglia (DAM) and neuroinflammation\u2010like microglia (NIM).\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Via network\u2010based prediction and population\u2010based validation, we identified that usage of ketorolac (a US Food and Drug Administration\u2013approved anti\u2010inflammatory medicine) was associated with reduced AD incidence in two independent patient databases.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Mechanistic observation showed that ketorolac treatment downregulated the Type\u2010I interferon signaling in patient induced pluripotent stem cell\u2013derived microglia, mechanistically supporting its protective effects in real\u2010world patient databases.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.14373","type":"journal-article","created":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T06:23:55Z","timestamp":1733466235000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Single\u2010microglia transcriptomic transition network\u2010based prediction and real\u2010world patient data validation identifies ketorolac as a repurposable drug for Alzheimer's disease"],"prefix":"10.1002","volume":"21","author":[{"given":"Jielin","family":"Xu","sequence":"first","affiliation":[{"name":"Cleveland Clinic Genome Center Lerner Research Institute Cleveland Clinic Cleveland Ohio USA"},{"name":"Genomic Medicine Institute Lerner Research Institute Cleveland Clinic Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqiang","family":"Song","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Genome Center Lerner Research Institute Cleveland Clinic Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenxing","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Population Health Sciences Weill Cornell Medicine Cornell University New York New York USA"},{"name":"Institute of Artificial Intelligence for Digital Health Weill Cornell Medicine Cornell University New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2674-0109","authenticated-orcid":false,"given":"Michael M.","family":"Danziger","sequence":"additional","affiliation":[{"name":"AI for Accelerated Healthcare and Life Sciences Discovery IBM Research\u2010Israel Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0187-5437","authenticated-orcid":false,"given":"Ehud","family":"Karavani","sequence":"additional","affiliation":[{"name":"AI for Accelerated Healthcare and Life Sciences Discovery IBM Research\u2010Israel Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8244-9551","authenticated-orcid":false,"given":"Chengxi","family":"Zang","sequence":"additional","affiliation":[{"name":"Department of Population Health Sciences Weill Cornell Medicine Cornell University New York New York USA"},{"name":"Institute of Artificial Intelligence for Digital Health Weill Cornell Medicine Cornell University New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Chen","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Genome Center Lerner Research Institute Cleveland Clinic Cleveland Ohio USA"},{"name":"Genomic Medicine Institute Lerner Research Institute Cleveland Clinic Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9079-104X","authenticated-orcid":false,"given":"Yichen","family":"Li","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Genome Center Lerner Research Institute Cleveland Clinic Cleveland Ohio USA"},{"name":"Genomic Medicine Institute Lerner Research Institute Cleveland Clinic Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9228-9270","authenticated-orcid":false,"given":"Isabela M Rivera","family":"Paz","sequence":"additional","affiliation":[{"name":"Genomic Medicine Institute Lerner Research Institute Cleveland Clinic Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4978-6035","authenticated-orcid":false,"given":"Dhruv","family":"Gohel","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Genome Center Lerner Research Institute Cleveland Clinic Cleveland Ohio USA"},{"name":"Genomic Medicine Institute Lerner Research Institute Cleveland Clinic Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Population Health Sciences Weill Cornell Medicine Cornell University New York New York USA"},{"name":"Institute of Artificial Intelligence for Digital Health Weill Cornell Medicine Cornell University New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yadi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Genome Center Lerner Research Institute Cleveland Clinic Cleveland Ohio USA"},{"name":"Genomic Medicine Institute Lerner Research Institute Cleveland Clinic Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Hou","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Genome Center Lerner Research Institute Cleveland Clinic Cleveland Ohio USA"},{"name":"Genomic Medicine Institute Lerner Research Institute Cleveland Clinic Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yishai","family":"Shimoni","sequence":"additional","affiliation":[{"name":"AI for Accelerated Healthcare and Life Sciences Discovery IBM Research\u2010Israel Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew A.","family":"Pieper","sequence":"additional","affiliation":[{"name":"Brain Health Medicines Center, Harrington Discovery Institute University Hospitals Cleveland Medical Center Cleveland Ohio USA"},{"name":"Department of Psychiatry Case Western Reserve University Cleveland Ohio USA"},{"name":"Geriatric Psychiatry GRECC Louis Stokes Cleveland VA Medical Center Cleveland Ohio USA"},{"name":"Institute for Transformative Molecular Medicine School of Medicine Case Western Reserve University Cleveland Ohio USA"},{"name":"Department of Neurosciences Case Western Reserve University School of Medicine Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianying","family":"Hu","sequence":"additional","affiliation":[{"name":"IBM T.J. Watson Research Center Yorktown Heights New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Population Health Sciences Weill Cornell Medicine Cornell University New York New York USA"},{"name":"Institute of Artificial Intelligence for Digital Health Weill Cornell Medicine Cornell University New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7616-9724","authenticated-orcid":false,"given":"Michal","family":"Rosen\u2010Zvi","sequence":"additional","affiliation":[{"name":"AI for Accelerated Healthcare and Life Sciences Discovery IBM Research\u2010Israel Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B.","family":"Leverenz","sequence":"additional","affiliation":[{"name":"Lou Ruvo Center for Brain Health Neurological Institute Cleveland Clinic Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Cummings","sequence":"additional","affiliation":[{"name":"Chambers\u2010Grundy Center for Transformative Neuroscience Department of Brain Health School of Integrated Health Sciences University of Nevada Las Vegas Las Vegas Nevada USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feixiong","family":"Cheng","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Genome Center Lerner Research Institute Cleveland Clinic Cleveland Ohio USA"},{"name":"Genomic Medicine Institute Lerner Research Institute Cleveland Clinic Cleveland Ohio USA"},{"name":"Department of Molecular Medicine Cleveland Clinic Lerner College of Medicine Case Western Reserve University Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13016"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2212948"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.13239"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/alzrt269"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2018.00699"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-018-0284-2"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-010-0433-4"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.845897"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.856376"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(15)70016-5"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.01.010"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.018"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.056653"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-023-00424-y"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1132939"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-021-02263-w"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2008762117"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-00764-7"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2019.03.003"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-018-0229-2"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/trc2.12350"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0969-x"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1663-x"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2188-x"},{"key":"e_1_2_8_27_1","article-title":"Multimodal single\u2010cell\/nucleus RNA sequencing data analysis uncovers molecular networks between disease\u2010associated microglia and astrocytes with implications for drug repurposing in Alzheimer's disease","author":"Xu J","year":"2021","journal-title":"Genome Res"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111717"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1014"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevLett.85.461"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08454"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.03.030"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-024-01664-w"},{"key":"e_1_2_8_34_1","unstructured":"ZhangB ZhuJ.Identification of Key Causal Regulators in Gene Networks.2013."},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-020-0153-3"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw377"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/jamiaopen\/ooaa048"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9681(87)90171-8"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwp436"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwab041"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/asn055"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2003.10.004"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1037\/a0019623"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-4356(00)00321-8"},{"key":"e_1_2_8_45_1","unstructured":"ShimoniY KaravaniE RavidS et\u00a0al.An Evaluation Toolkit to Guide Model Selection and Cohort Definition in Causal Inference. arXiv; 2019 . Available from:http:\/\/arxiv.org\/abs\/1906.00442"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1086\/341527"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-43929-1"},{"key":"e_1_2_8_48_1","doi-asserted-by":"crossref","DOI":"10.1136\/bmj-2021-068414","article-title":"Risk of persistent and new clinical sequelae among adults aged 65 years and older during the post\u2010acute phase of SARS\u2010CoV\u20102 infection: retrospective cohort study","volume":"376","author":"Cohen K","year":"2022","journal-title":"BMJ"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.2217\/cer-2020-0013"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.3697"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42256-020-00276-w"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1989.10478874"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1214\/ss\/1032280214"},{"key":"e_1_2_8_54_1","doi-asserted-by":"crossref","unstructured":"KlineA LuoY.PsmPy: A Package for Retrospective Cohort Matching in Python. In:2022 44th Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC).IEEE;2022:1354\u20101357.","DOI":"10.1109\/EMBC48229.2022.9871333"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.21105\/joss.01317"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty560"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz114"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks042"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0071-9"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.27"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/75556"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201800926R"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-022-00535-x"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23522"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2014.10.011"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-7-48"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.01.022"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12849"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12821"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0403921101"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-180759"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.09.033"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.09.030"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-021-01126-5"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-021-00773-z"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01024-z"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201910606"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1097409"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2020.140428"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2014.05.029"},{"key":"e_1_2_8_81_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.183"},{"key":"e_1_2_8_82_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3268-10.2011"},{"key":"e_1_2_8_83_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-022-01128-z"},{"key":"e_1_2_8_84_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01149-1"},{"key":"e_1_2_8_85_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00875-2"},{"key":"e_1_2_8_86_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00976-y"},{"key":"e_1_2_8_87_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-023-01072-w"},{"key":"e_1_2_8_88_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.103994"},{"key":"e_1_2_8_89_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.068943"},{"key":"e_1_2_8_90_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2023.01.004"},{"key":"e_1_2_8_91_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2016.206"},{"key":"e_1_2_8_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.03.032"},{"key":"e_1_2_8_93_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph15020109"},{"key":"e_1_2_8_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2010.08.020"},{"key":"e_1_2_8_95_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.050762"},{"key":"e_1_2_8_96_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-59917-0"},{"key":"e_1_2_8_97_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI133737"},{"key":"e_1_2_8_98_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.03.018"},{"key":"e_1_2_8_99_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.07.004"},{"key":"e_1_2_8_100_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1862-5"},{"key":"e_1_2_8_101_1","doi-asserted-by":"publisher","DOI":"10.15252\/msb.20209620"},{"key":"e_1_2_8_102_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.08.037"},{"key":"e_1_2_8_103_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19737-2"},{"key":"e_1_2_8_104_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.10.036"},{"key":"e_1_2_8_105_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12540"},{"key":"e_1_2_8_106_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-023-00823-1"},{"key":"e_1_2_8_107_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad8373"},{"key":"e_1_2_8_108_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1136-17.2017"},{"key":"e_1_2_8_109_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2023.101175"},{"key":"e_1_2_8_110_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2024.2340408"},{"key":"e_1_2_8_111_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0332-9"},{"key":"e_1_2_8_112_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13847"},{"key":"e_1_2_8_113_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-021-00138-z"},{"key":"e_1_2_8_114_1","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/s41593-022-01251-x","article-title":"Integrative in situ mapping of single\u2010cell transcriptional states and tissue histopathology in a mouse model of Alzheimer's disease","volume":"26","author":"Zeng H","year":"2023","journal-title":"Nat Neurosci"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.14373","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T06:07:53Z","timestamp":1762495673000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.14373"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,6]]},"references-count":113,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1002\/alz.14373"],"URL":"https:\/\/doi.org\/10.1002\/alz.14373","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,6]]},"assertion":[{"value":"2024-04-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14373"}}