{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T17:01:29Z","timestamp":1791478889900,"version":"4.3.4"},"reference-count":24,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T00:00:00Z","timestamp":1682553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>\u03b2\u2010Synuclein is an emerging synaptic blood biomarker for Alzheimer's disease (AD) but differences in \u03b2\u2010synuclein levels in preclinical AD and its association with amyloid and tau pathology have not yet been studied.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We measured plasma \u03b2\u2010synuclein levels in cognitively unimpaired individuals with positive A\u03b2\u2010PET (i.e., preclinical AD, <jats:italic>N<\/jats:italic>\u00a0=\u00a048) or negative A\u03b2\u2010PET (<jats:italic>N<\/jats:italic>\u00a0=\u00a061), A\u03b2\u2010positive patients with mild cognitive impairment (MCI, <jats:italic>N<\/jats:italic>\u00a0=\u00a036), and A\u03b2\u2010positive AD dementia (<jats:italic>N<\/jats:italic>\u00a0=\u00a085). Amyloid (A) and tau (T) pathology were assessed by [<jats:sup>18<\/jats:sup>F]flutemetamol and [<jats:sup>18<\/jats:sup>F]RO948 PET.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Plasma \u03b2\u2010synuclein levels were higher in preclinical AD and even higher in MCI and AD dementia. Stratification according to amyloid\/tau pathology revealed higher \u03b2\u2010synuclein in A<jats:sup>+<\/jats:sup>T<jats:sup>\u2212<\/jats:sup> and A<jats:sup>+<\/jats:sup>T<jats:sup>+<\/jats:sup> subjects compared with A<jats:sup>\u2212<\/jats:sup>T<jats:sup>\u2212<\/jats:sup>. Plasma \u03b2\u2010synuclein levels were related to tau and A\u03b2 pathology and associated with temporal cortical thinning and cognitive impairment.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Our data indicate that plasma \u03b2\u2010synuclein might track synaptic dysfunction, even during the preclinical stages of AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>HIGHLIGHTS<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Plasma \u03b2\u2010synuclein is already higher in preclinical AD.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Plasma \u03b2\u2010synuclein is higher in MCI and AD dementia than in preclinical AD.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>A\u03b2\u2010 and tau\u2010PET SUVRs are associated with plasma \u03b2\u2010synuclein levels.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Plasma \u03b2\u2010synuclein is already higher in tau\u2010PET negative subjects.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Plasma \u03b2\u2010synuclein is related to temporal cortical atrophy and cognitive impairment.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.13103","type":"journal-article","created":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T04:59:42Z","timestamp":1682571582000},"page":"5095-5102","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Higher plasma \u03b2\u2010synuclein indicates early synaptic degeneration in Alzheimer's disease"],"prefix":"10.1002","volume":"19","author":[{"given":"Patrick","family":"Oeckl","sequence":"first","affiliation":[{"name":"German Center for Neurodegenerative Diseases e.V. (DZNE)  Ulm Germany"},{"name":"Department of Neurology Ulm University Hospital  Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shorena","family":"Janelidze","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Malm\u00f6 Clinical Memory Research Unit Lund University  Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Halbgebauer","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases e.V. (DZNE)  Ulm Germany"},{"name":"Department of Neurology Ulm University Hospital  Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Stomrud","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Malm\u00f6 Clinical Memory Research Unit Lund University  Malm\u00f6 Sweden"},{"name":"Memory Clinic Sk\u00e5ne University Hospital  Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Palmqvist","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Malm\u00f6 Clinical Memory Research Unit Lund University  Malm\u00f6 Sweden"},{"name":"Memory Clinic Sk\u00e5ne University Hospital  Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Otto","sequence":"additional","affiliation":[{"name":"Department of Neurology Ulm University Hospital  Ulm Germany"},{"name":"University Clinic and Polyclinic for Neurology Martin\u2010Luther\u2010University Halle\u2010Wittenberg  Halle Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oskar","family":"Hansson","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Malm\u00f6 Clinical Memory Research Unit Lund University  Malm\u00f6 Sweden"},{"name":"Memory Clinic Sk\u00e5ne University Hospital  Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410300410"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/1177271920950319"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.9b00824"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp\u20102020\u2010324306"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M116.059915"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/JNNP\u20102022\u2010329124"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51402"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/S41591\u2010021\u201001382\u2010X"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ALZ.12790"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/JAMA.2020.12134"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.books.9780890425596"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.018"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1515\/CCLM\u20102021\u20100651"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/S41467\u2010022\u201034129\u20104"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/JAMANEUROL.2020.0989"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.2967\/JNUMED.114.148981"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ANA.24711"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/BRAIN\/AWAC343"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/BRAIN\/AWV283"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000012853"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JALZ.2018.12.019"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26360"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMOA2212948"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/BRAIN\/AWAA395"}],"container-title":["Alzheimer's &amp; 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