{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T16:28:08Z","timestamp":1793204888815,"version":"4.5.0"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["SG\u201020\u2010690363\u2010DIAN"],"award-info":[{"award-number":["SG\u201020\u2010690363\u2010DIAN"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005224","name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005224","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":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>\u03b2\u2010synuclein is a promising blood marker to track synaptic degeneration in Alzheimer's disease (AD) but changes in preclinical AD are unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We investigated serum \u03b2\u2010synuclein in 69 cognitively unimpaired mutation non\u2010carriers, 78 cognitively unimpaired AD mutation carriers (asymptomatic AD), and 31 symptomatic mutation carriers from the Dominantly Inherited Alzheimer Network.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\u03b2\u2010synuclein levels were already higher in asymptomatic AD mutation carriers compared to non\u2010carriers and highest in symptomatic carriers. Longitudinal trajectories and correlation analyses indicated that \u03b2\u2010synuclein levels start to rise after amyloid deposition preceding axonal degeneration, brain atrophy and hypometabolism, and cognitive decline. \u03b2\u2010synuclein levels were associated with cognitive impairment and gradually increased with declining cognition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Our study supports the use of blood \u03b2\u2010synuclein to track synaptic changes in preclinical AD and as a surrogate marker for cognitive impairment which might be used in early diagnosis and to support patient selection and monitoring of treatment effects in clinical trials.<\/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>Blood \u03b2\u2010synuclein levels were already higher in asymptomatic Alzheimer's disease (AD) mutation carriers.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Blood \u03b2\u2010synuclein levels were highest in symptomatic AD mutation carriers.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Blood \u03b2\u2010synuclein levels start to rise 11 years before symptom onset.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Rise of \u03b2\u2010synuclein precedes axonal degeneration, brain atrophy, and cognitive decline.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\u03b2\u2010synuclein levels gradually increased with declining cognition.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70146","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T05:36:39Z","timestamp":1744263399000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Early increase of the synaptic blood marker \u03b2\u2010synuclein in asymptomatic autosomal dominant Alzheimer's disease"],"prefix":"10.1002","volume":"21","author":[{"given":"Patrick","family":"Oeckl","sequence":"first","affiliation":[{"name":"Department of Neurology Ulm University Hospital Ulm Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE) Ulm Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Mayer","sequence":"additional","affiliation":[{"name":"Institute for Epidemiology and Medical Biometry University of Ulm Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall J.","family":"Bateman","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University School of Medicine Saint Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory S.","family":"Day","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic in Florida Jacksonville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick C.","family":"Fox","sequence":"additional","affiliation":[{"name":"The Dementia Research Centre Department of Neurodegenerative Disease UCL Queen Square Institute of Neurology London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward D.","family":"Huey","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Human Behavior Alpert Medical School of Brown University Providence Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Ibanez","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Department of Neurology and NeuroGenomics and Informatics Center Washington University Saint Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Ikeuchi","sequence":"additional","affiliation":[{"name":"Brain Research Institute Niigata University Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Jucker","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) T\u00fcbingen T\u00fcbingen Germany"},{"name":"Hertie\u2010Institute for Clinical Brain Research University of T\u00fcbingen T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae\u2010Hong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurology Asan Medical Center University of Ulsan College of Medicine Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Levin","sequence":"additional","affiliation":[{"name":"Department of Neurology LMU University Hospital LMU Munich Munich Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE) Munich Munich Germany"},{"name":"Munich Cluster for Systems Neurology (SyNergy) Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge J.","family":"Llibre\u2010Guerra","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University School of Medicine Saint Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Lopera","sequence":"additional","affiliation":[{"name":"Neuroscience Group of Antioquia (GNA) Medicine Faculty Antioquia University Medell\u00edn Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"McDade","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University School of Medicine Saint Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Neurology and the Knight Alzheimer Disease Research Center Washington University Saint Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiki","family":"Niimi","sequence":"additional","affiliation":[{"name":"Unit for Early and Exploratory Clinical Development The University of Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jee Hoon","family":"Roh","sequence":"additional","affiliation":[{"name":"Departments of Neurology and Physiology Korea University Anam Hospital Korea University College of Medicine Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"S\u00e1nchez\u2010Valle","sequence":"additional","affiliation":[{"name":"Alzheimer's Disease and Other Cognitive Disorders Unit. Hospital Cl\u00ednic de Barcelona FRCB\u2010IDIBAPS University of Barcelona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R.","family":"Schofield","sequence":"additional","affiliation":[{"name":"Neuroscience Research Australia Sydney New South Wales Australia"},{"name":"School of Biomedical Sciences University of New South Wales Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4273-4267","authenticated-orcid":false,"given":"Markus","family":"Otto","sequence":"additional","affiliation":[{"name":"Department of Neurology Martin\u2010Luther\u2010University Halle\u2010Wittenberg Halle (Saale) Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Dominantly Inherited Alzheimer Network","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ALZ.12582"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/S41380\u2010023\u201002376\u20106"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMOA2212948"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.9b00824"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13103"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13046"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12790"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/S41591\u2010020\u20100781\u2010Z"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.4155\/CLI.12.93"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMOA1202753"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/S41591\u2010018\u20100304\u20103"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/S41593\u2010023\u201001359\u20108"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-33226-6_13"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JALZ.2018.12.019"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/S41591\u2010023\u201002476\u20104"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ALZ.079855"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ALZ.12879"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/BRAIN\/AWAA395"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1074069"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26360"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/BRAINCOMMS\/FCAD280"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410300410"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1001\/JAMA.2023.13239"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2015.05.012"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000006277"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.70146","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T20:58:44Z","timestamp":1759957124000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.70146"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4]]},"references-count":25,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1002\/alz.70146"],"URL":"https:\/\/doi.org\/10.1002\/alz.70146","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4]]},"assertion":[{"value":"2024-11-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70146"}}