{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T07:16:54Z","timestamp":1783322214673,"version":"3.54.6"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T00:00:00Z","timestamp":1776556800000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/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"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF18OC0033928"],"award-info":[{"award-number":["NNF18OC0033928"]}],"id":[{"id":"10.13039\/501100009708","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":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>\n                      The rs11218343 is a non\u2010coding variant of genome\u2010wide significance for sporadic Alzheimer's disease (AD) with one of the most protective effects known to date. It localizes to\n                      <jats:italic>SORL1<\/jats:italic>\n                      , encoding the AD risk factor Sortilin\u2010related receptor with A type repeats (SORLA). Still, the functional significance of rs11218343 for AD\u2010related processes remains unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We used induced pluripotent stem cell (iPSC) lines from donors, or genome\u2010engineered to carry major and minor rs11218343 alleles, to study the impact of rs11218343 on cellular activities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>We show that rs11218343 is uniquely linked to functional expression of SORLA in microglia, with increased expression in the protective allele correlating with reduced pro\u2010inflammatory responses. These anti\u2010inflammatory effects are seen in donor lines but not in single nucleotide polymorphism (SNP) \u2010engineered isogenic lines, arguing that this polymorphism alone is insufficient but acting context\u2010dependent.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>\n                      Our data infer genetically defined expression of\n                      <jats:italic>SORL1<\/jats:italic>\n                      in microglia as a determinant of protection from pro\u2010inflammatory stimulation, a function likely encoded by a haplotype linked to rs11218343.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71390","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T03:20:05Z","timestamp":1776655205000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Alzheimer's disease risk single nucleotide polymorphism rs11218343 is linked to functional expression of\n                    <i>SORL1<\/i>\n                    in microglia"],"prefix":"10.1002","volume":"22","author":[{"given":"Malgorzata","family":"Gorniak\u2010Walas","sequence":"first","affiliation":[{"name":"Department of Biomedicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narasimha S.","family":"Telugu","sequence":"additional","affiliation":[{"name":"Technology Platform for Pluripotent Stem Cells Max\u2010Delbrueck\u2010Center for Molecular Medicine in the Helmholtz Association  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ina\u2010Maria","family":"Rudolph","sequence":"additional","affiliation":[{"name":"Molecular Cardiovascular Research Max\u2010Delbrueck\u2010Center for Molecular Medicine in the Helmholtz Association  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Diecke","sequence":"additional","affiliation":[{"name":"Technology Platform for Pluripotent Stem Cells Max\u2010Delbrueck\u2010Center for Molecular Medicine in the Helmholtz Association  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas E.","family":"Willnow","sequence":"additional","affiliation":[{"name":"Department of Biomedicine Aarhus University  Aarhus Denmark"},{"name":"Molecular Cardiovascular Research Max\u2010Delbrueck\u2010Center for Molecular Medicine in the Helmholtz Association  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2020.08.003"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi052120v"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2015.00109"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2272-11.2012"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0206-16.2016"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0427-15.2015"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0503689102"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4946-05.2006"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-024-01104-7"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4397"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.2014.988707"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2022.0389"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.70009"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24659"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70591"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2017.87"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2012.15"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01208-7"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1943"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2802"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01024-z"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0358-2"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-021-01294-4"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-023-02670-1"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2408262121"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2022.0377"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0058618"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-016-9780-y"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aay0793"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2021.102406"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.05.029"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-018-0103-2"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-018-0297-x"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.12.012"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2011.788"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3960-09.2009"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2015.02.004"}],"container-title":["Alzheimer's 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