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We recently reported an AD\u2010associated CD83(+) microglia subtype associated with increased immunoglobulin G4 (IgG4) in the transverse colon (TC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We used immunohistochemistry (IHC), IgG4 repertoire profiling, and brain organoid experiments to explore this association.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>CD83(+) microglia in the superior frontal gyrus (SFG) are associated with elevated IgG4 and human cytomegalovirus (HCMV) in the TC, anti\u2010HCMV IgG4 in cerebrospinal fluid, and both HCMV and IgG4 in the SFG and vagal nerve. This association was replicated in an independent AD cohort. HCMV\u2010infected cerebral organoids showed accelerated AD pathophysiological features (A\u03b242 and pTau\u2010212) and neuronal death.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Findings indicate complex, cross\u2010tissue interactions between HCMV and the adaptive immune response associated with CD83(+) microglia in persons with AD. This may indicate an opportunity for antiviral therapy in persons with AD and biomarker evidence of HCMV, IgG4, or CD83(+) microglia.<\/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>Cross\u2010tissue interaction between HCMV and the adaptive immune response in a subset of persons with AD.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Presence of CD83(+) microglial associated with IgG4 and HCMV in the gut.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>CD83(+) microglia are also associated presence of HCMV and IgG4 in the cortex and vagal nerve.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Replication of key association in an independent cohort of AD subjects.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>HCMV infection of cerebral organoids accelerates the production of AD neuropathological features.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.14401","type":"journal-article","created":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T07:06:40Z","timestamp":1734592000000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Alzheimer's disease\u2010associated CD83(+) microglia are linked with increased immunoglobulin G4 and human cytomegalovirus in the gut, vagal nerve, and brain"],"prefix":"10.1002","volume":"21","author":[{"given":"Benjamin P.","family":"Readhead","sequence":"first","affiliation":[{"name":"ASU\u2010Banner Neurodegenerative Disease Research Center Arizona State University  Tempe Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego F.","family":"Mastroeni","sequence":"additional","affiliation":[{"name":"ASU\u2010Banner Neurodegenerative Disease Research Center Arizona State University  Tempe Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"ASU\u2010Banner Neurodegenerative Disease Research Center Arizona State University  Tempe Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria A.","family":"Sierra","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Weill Cornell Medicine  New York New York 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