{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T10:01:39Z","timestamp":1792058499475,"version":"4.4.0"},"reference-count":53,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T00:00:00Z","timestamp":1743033600000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100011707","name":"PSP Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011707","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021686","name":"Dementias Platform UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021686","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UU_00030\/14;MR\/T033371\/1"],"award-info":[{"award-number":["MC_UU_00030\/14;MR\/T033371\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017510","name":"UK Dementia Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017510","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008539","name":"CurePSP","doi-asserted-by":"publisher","award":["689\u20102024\u201001\u2010Pipeline"],"award-info":[{"award-number":["689\u20102024\u201001\u2010Pipeline"]}],"id":[{"id":"10.13039\/100008539","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018703","name":"HORIZON EUROPE European Innovation Council","doi-asserted-by":"publisher","award":["101053962"],"award-info":[{"award-number":["101053962"]}],"id":[{"id":"10.13039\/100018703","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["#2023\u201000356"],"award-info":[{"award-number":["#2023\u201000356"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["#2022\u201001018"],"award-info":[{"award-number":["#2022\u201001018"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["#2019\u201002397"],"award-info":[{"award-number":["#2019\u201002397"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018956","name":"NIHR Cambridge Biomedical Research Centre","doi-asserted-by":"publisher","award":["BRC\u20101215\u201020014;NIHR203312"],"award-info":[{"award-number":["BRC\u20101215\u201020014;NIHR203312"]}],"id":[{"id":"10.13039\/501100018956","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["103838"],"award-info":[{"award-number":["103838"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["220258"],"award-info":[{"award-number":["220258"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011707","name":"PSP Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011707","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":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Blood\u2010based biomarkers have the potential to support early and accurate diagnoses of neurodegenerative diseases, which are sensitive to molecular pathology and are predictive of outcome. We evaluated a novel multiplex proteomic method in people with diverse neurodegenerative diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Serum from people with Alzheimer's disease (\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a036), Lewy body dementia (\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a034), frontotemporal dementia (\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a036), and progressive supranuclear palsy (\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a036) and age\u2010matched controls (\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a030) was analyzed with the nucleic acid linked immuno\u2010sandwich assay (NULISA) central nervous system panel (\u2248 120 analytes) and inflammation panel (250 analytes). Biomarkers were compared across groups and included as predictors of survival.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>The NULISA panels demonstrated high sensitivity and reliability for detecting multiple biomarkers across neurodegenerative disorders. There were condition\u2010specific proteomic biomarkers, while neurofilament light chain, corticotropin\u2010releasing hormone, CD276, and a data\u2010driven inflammation pattern were significant transdiagnostic outcome predictors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>The sensitive NULISA multiplex approach supports differential diagnosis and target identification, with prognostically informative dementia\u2010related biomarkers.<\/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 the novel technology nucleic acid linked immuno\u2010sandwich assay (NULISA) in people with diverse neurodegenerative diseases, which demonstrated high sensitivity and reliability for detecting multiple biomarkers in serum samples.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We compared the NULISA central nervous system serum results to single molecule array (Simoa) plasma assays for phosphorylated tau (p\u2010tau)217, p\u2010tau231, neurofilament light chain (NfL), and glial fibrillary acidic protein, finding strong correlations.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Increased levels of serum NfL were identified across all patient groups and most elevated in the frontotemporal dementia (FTD) and progressive supranuclear palsy (PSP) cohorts, while p\u2010tau epitopes were the most significant markers in patients with Alzheimer's disease (AD) and Lewy body dementia.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Patients with FTD and PSP showed upregulation of many inflammation markers, compared to controls and patients with AD.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We found condition\u2010specific proteomic biomarkers, while NfL, corticotropin\u2010releasing hormone, CD276, and data\u2010driven immune signatures were significant transdiagnostic predictors of clinical outcomes (survival rates).<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70116","type":"journal-article","created":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T23:53:42Z","timestamp":1743292422000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Novel blood\u2010based proteomic signatures across multiple neurodegenerative diseases"],"prefix":"10.1002","volume":"21","author":[{"given":"Robert","family":"Durcan","sequence":"first","affiliation":[{"name":"Department of Clinical Neurosciences University of Cambridge and Cambridge University Hospitals NHS Trust  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Heslegrave","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Swann","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Goddard","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences University of Cambridge and Cambridge University Hospitals NHS Trust  Cambridge UK"},{"name":"UK Dementia Research Institute University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonidas","family":"Chouliaras","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander G.","family":"Murley","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences University of Cambridge and Cambridge University Hospitals NHS Trust  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Savulich","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Richard","family":"Bevan\u2010Jones","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Owen","family":"Swann","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Ashton","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology The Sahlgrenska Academy University of Gothenburg  M\u00f6lndal Sweden"},{"name":"Banner Alzheimer's Institute University of Arizona  Phoenix Arizona USA"},{"name":"Banner Sun Health Research Institute  Sun City Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology The Sahlgrenska Academy University of Gothenburg  M\u00f6lndal Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital  M\u00f6lndal Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"McEwan","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute University College London  London UK"},{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology The Sahlgrenska Academy University of Gothenburg  M\u00f6lndal Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital  M\u00f6lndal Sweden"},{"name":"Department of Neurodegenerative Disease UCL Institute of Neurology  London UK"},{"name":"Hong Kong Center for Neurodegenerative Diseases  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B.","family":"Rowe","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences University of Cambridge and Cambridge University Hospitals NHS Trust  Cambridge UK"},{"name":"Medical Research Council Cognition and Brain Sciences Unit University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John T.","family":"O'Brien","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maura","family":"Malpetti","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences University of Cambridge and Cambridge University Hospitals NHS Trust  Cambridge UK"},{"name":"UK Dementia Research Institute University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195\u2010023\u201001314\u20106"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582\u2010024\u201000942\u20102"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000200878"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.30019"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29766"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.5319"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp\u20102021\u2010327788"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(21)00214\u20103"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.70003"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201023620\u2010z"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010021\u201002275\u20106"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2024.5017"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201042834\u2010x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024\u2010024\u201000753\u20105"},{"key":"e_1_2_8_16_1","doi-asserted-by":"crossref","unstructured":"AshtonNJ BenedetAL Di MolfettaG et\u00a0al.Biomarker discovery in Alzheimer's and neurodegenerative diseases using nucleic acid\u2010linked immuno\u2010sandwich assay.medRxiv;2024. doi:10.1101\/2024.07.29.24311079","DOI":"10.1002\/alz.14621"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14413"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcaf004"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.005"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.008.The"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26987"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31821103e6"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr179"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004058"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2574\u201018.2019"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa088"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww340"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.08.005"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/practneurol\u20102021\u2010003310"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1101\/525642"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0000000000011848"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.290"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010022\u201001942\u20109"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awae269"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2016.6117"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2022.06.004"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749\u20106632.1987.tb24964.x"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.168.6.679"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12463"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2014.10.031"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201041122\u2010y"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcae414"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.104202"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301\u20100082(99)00033\u20107"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231810970"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582\u2010019\u20100231\u2010z"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010021\u201094360\u20109"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1177\/0891988706286226"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100404.2011.01524.x"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1177\/13872877241283677"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tjpad.2024.100013"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398\u2010024\u201003084\u20107"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195\u2010024\u201001503\u2010x"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13163"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.70116","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alz.70116","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.70116","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T10:17:57Z","timestamp":1789553877000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.70116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3]]},"references-count":53,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["10.1002\/alz.70116"],"URL":"https:\/\/doi.org\/10.1002\/alz.70116","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.12.28.24319680","asserted-by":"object"}]},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3]]},"assertion":[{"value":"2024-12-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70116"}}