{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T04:45:30Z","timestamp":1782535530800,"version":"3.54.5"},"reference-count":32,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp; Dementia"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>\n                      A deep multi\u2010omic analysis of\n                      <jats:italic>post mortem<\/jats:italic>\n                      human brains has identified a new co\u2010expression protein network \u2013 Module 42 (M42), strongly corelated with Alzheimer's disease (AD) pathology. M42 comprises 32 transmembrane and extracellular matrix (ECM)\u2010associated proteins, including the amyloid precursor protein (APP) and apolipoprotein E (apoE), and its members have been implicated in amyloid beta (A\u03b2) pathology. We systematically evaluated the A\u03b2\u2010independent effects of M42 on immune function in vitro.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Recombinant M42 proteins were expressed and purified. Their effects on phagocytosis, intracellular signaling, and cell viability were assessed in human induced pluripotent stem cell\u2010derived macrophages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Treatment with Midkine (MDK) reduced phagocytosis, while treatment with the ectodomain of Transmembrane protein with EGF\u2010like and two follistatin\u2010like domains 2 (TMEFF2) had the opposite effect. Both proteins promoted intracellular Ca\n                      <jats:sup>2+<\/jats:sup>\n                      signaling, and TMEFF2 also suppressed Syk kinase activity. No M42 proteins had an effect on viability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Our results suggest an additional role for M42 in AD via regulating immune functions.<\/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>We tested M42 proteins for their effects on immune functions in vitro.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Five proteins altered phagocytosis, and seven altered Ca\n                            <jats:sup>2+<\/jats:sup>\n                            signaling.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            MDK and TMEFF2 ectodomain had an effect on both phagocytosis and Ca\n                            <jats:sup>2+<\/jats:sup>\n                            signaling.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71215","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T20:17:53Z","timestamp":1773001073000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Assessing A\u03b2\u2010independent effects of Module 42 on immune function in vitro"],"prefix":"10.1002","volume":"22","author":[{"given":"Ishita","family":"Ajith","sequence":"first","affiliation":[{"name":"Centre for Medicines Discovery  Oxford UK"},{"name":"Institute for Stroke and Dementia Research (ISD) University Hospital LMU Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Souvika","family":"Bakshi","sequence":"additional","affiliation":[{"name":"Centre for Medicines Discovery  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Mead","sequence":"additional","affiliation":[{"name":"Centre for Medicines Discovery  Oxford UK"},{"name":"Alzheimer's Research UK Oxford Drug Discovery Institute  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Opher","family":"Gileadi","sequence":"additional","affiliation":[{"name":"Centre for Medicines Discovery  Oxford UK"},{"name":"Centre for Molecular Medicine Karolinska Institutet and Karolinska Hospital  Solna Stockholm Sweden"},{"name":"Department of Medicine Solna Structural Genomics Consortium Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittorio L.","family":"Katis","sequence":"additional","affiliation":[{"name":"Centre for Medicines Discovery  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul E.","family":"Brennan","sequence":"additional","affiliation":[{"name":"Centre for Medicines Discovery  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Emory\u2010Sage\u2010SGC\u2010Jax TREAT\u2010AD Center","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4525-0460","authenticated-orcid":false,"given":"Katerina O.","family":"Gospodinova","sequence":"additional","affiliation":[{"name":"Centre for Medicines Discovery  Oxford UK"},{"name":"Alzheimer's Research UK Oxford Drug Discovery Institute  Oxford 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