{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:21:03Z","timestamp":1790691663082,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100012331","name":"Agentschap Innoveren en Ondernemen","doi-asserted-by":"publisher","award":["PRISMA"],"award-info":[{"award-number":["PRISMA"]}],"id":[{"id":"10.13039\/100012331","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010676","name":"H2020 Societal Challenges","doi-asserted-by":"publisher","award":["874707"],"award-info":[{"award-number":["874707"]}],"id":[{"id":"10.13039\/100010676","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":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Alzheimer's disease is a severe neurodegenerative disorder, with multifactorial mechanisms of disease development and progression. Evidence from genetic association studies, animal models, and clinical investigation suggests a neuroimmunological component to disease, with links to the peripheral immune system.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Here we applied a systems immunology approach to determine the immunological correlates of Alzheimer's disease. Using high\u2010dimensional flow cytometry and machine learning, we comprehensively assessed the cellular component of the peripheral immune system in a well\u2010characterized cohort of 184 Alzheimer's patients and 105 healthy spouses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Using this approach, Alzheimer's patients demonstrated a disturbance in B cell maturation, a feature that was associated not only with disease status but also with cognitive decline. This effect was age and environmental exposure independent, suggesting a disease\u2010intrinsic relationship between Alzheimer's disease and B cell maturation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These results provide an underexplored avenue for improving both mechanistic understanding and therapeutic design in Alzheimer's disease.<\/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>A systems immunology analysis on a cohort of 184 patients with Alzheimer's disease (AD) and 105 healthy spouses.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>AD demonstrated a defect in B cell maturation, associated with more cognitive decline.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The B cell maturation association was age and environmental exposure independent.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Additional peripheral immunological changes were associated with AD.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70952","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T10:04:15Z","timestamp":1764065055000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A systems immunology analysis of Alzheimer's disease reveals an age\u2010 and environmental exposure\u2010independent disturbance in B cell maturation"],"prefix":"10.1002","volume":"21","author":[{"given":"Stephanie","family":"Humblet\u2010Baron","sequence":"first","affiliation":[{"name":"Department of Microbiology KU Leuven Immunology and Transplantation  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Neurosciences KU Leuven Laboratory for Cognitive Neurology  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Veiga","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julika","family":"Neumann","sequence":"additional","affiliation":[{"name":"Department of Microbiology KU Leuven Immunology and Transplantation  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Prezzemolo","sequence":"additional","affiliation":[{"name":"Department of Microbiology KU Leuven Immunology and Transplantation  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Pasciuto","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences University of Antwerp  Antwerp Belgium"},{"name":"Center for Molecular Neurology VIB  Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rik","family":"Vandenberghe","sequence":"additional","affiliation":[{"name":"Department of Neurosciences KU Leuven Laboratory for Cognitive Neurology  Leuven Belgium"},{"name":"Neurology service UZ Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidia","family":"Yshii","sequence":"additional","affiliation":[{"name":"Department of Neurosciences KU Leuven Laboratory for Cognitive 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