{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T20:44:08Z","timestamp":1788381848277,"version":"build-2803163510"},"reference-count":75,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/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\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["ID 259373024 \u2013 CRC\/TRR 167 (B05)"],"award-info":[{"award-number":["ID 259373024 \u2013 CRC\/TRR 167 (B05)"]}],"id":[{"id":"10.13039\/501100001659","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>Tryptophan metabolism is increasingly implicated in Alzheimer's disease (AD), particularly through aryl hydrocarbon receptor (AhR) ligands that influence neuroinflammation. However, their relationships with core AD pathology\u2014amyloid\u2010\u03b2 (A) and tau (T) deposition\u2014and associated immune\u2013proteomic alterations remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We performed integrative multi\u2010omics\/high\u2010dimensional profiling of cerebrospinal fluid (CSF) and peripheral blood from A\u2010T\u2010 (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a019) and A+T+ (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a035) individuals, classified based on CSF A\u03b2 and pTau181 levels. Analyses included targeted metabolomics, mass cytometry, and NULISA\u2010based proteomics, and inter\u2010compartmental correlation analysis. Brain\u2010derived tryptophan catabolism was investigated using single\u2010nucleus RNA sequencing (snRNA\u2010seq).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Thirteen differentially expressed CSF proteins in A+T+ individuals correlated positively with tryptophan metabolites and pyroglutamate, and negatively with regulatory T cells, isobutyrate, and dendritic cells. Similar patterns were observed in blood. snRNA\u2010seq suggested partial brain origin of metabolites.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Our findings highlight conserved immune\u2013metabolic\u2013proteomic signatures in AD and implicate tryptophan metabolism as a cross\u2010compartmental factor relevant for biomarker and therapeutic development.<\/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>Thirteen cerebrospinal fluid (CSF) proteins involved in metabolism and neuronal function link to Alzheimer's disease (AD) pathology<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Intergrative analysis reveals shared and compartment\u2010specific AD signatures<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Tryptophan\u2010kynurenine metabolites correlate with AD pathology<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Indole metabolites show CSF\u2010plasma coupling in A+T+ individuals<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Immune signatures diverge across CSF (regulatory T cells [Tregs], dendritic cells [DCs]) and blood (B and myeloid cells)<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71359","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T03:01:15Z","timestamp":1776222075000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Immune\u2013proteo\u2013metabolomic changes link to A\u03b2 and tau pathology in Alzheimer disease"],"prefix":"10.1002","volume":"22","author":[{"given":"Meng","family":"Wang","sequence":"first","affiliation":[{"name":"Experimental and Clinical Research Center a cooperation between the Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association and Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association (MDC)  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Buthut","sequence":"additional","affiliation":[{"name":"Department of Neurology and Experimental Neurology Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE)  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Meinhardt","sequence":"additional","affiliation":[{"name":"Department of Neuropathology Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolin","family":"Otto","sequence":"additional","affiliation":[{"name":"Department of Neurology and Experimental Neurology Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerardina","family":"Gallaccio","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center a cooperation between the Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association and Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association (MDC)  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila","family":"Fern\u00e1ndez\u2010Zapata","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center a cooperation between the Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association and Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association (MDC)  Berlin Germany"},{"name":"III. 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