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The presynaptic protein \u03b2\u2010synuclein is elevated in the blood of adults with DS. This study evaluates the positioning of these changes relative to changes in pathophysiological blood biomarkers along the AD continuum.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We quantified serum \u03b2\u2010synuclein using immunoprecipitation\u2013mass spectrometry in a cross\u2010sectional cohort (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0131) spanning the AD continuum in adults with DS (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a088) and cognitively unimpaired euploid controls (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a043).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      \u03b2\u2010synuclein levels were elevated in individuals with DS (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.001), preceding symptom onset by two decades and changes in other blood biomarkers (tau phosphorylated at threonine 217, neurofilament light, glial fibrillary acidic protein) by several years. Higher \u03b2\u2010synuclein was associated with cortical atrophy (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.001) and hypometabolism (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.001) in AD\u2010vulnerable regions and reduced episodic memory (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.009).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These findings consolidate \u03b2\u2010synuclein as an early blood\u2010based biomarker of synaptic dysfunction and provide insight into early AD\u2010related mechanisms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71860","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T06:47:00Z","timestamp":1790059620000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Changes in serum \u03b2\u2010synuclein precede blood biomarkers of Alzheimer pathology in Down syndrome"],"prefix":"10.1002","volume":"22","author":[{"given":"Alba","family":"Cervantes Gonz\u00e1lez","sequence":"first","affiliation":[{"name":"Memory Unit, IR SANT PAU Hospital de la Santa Creu i Sant Pau  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Neurodegenerativas (CIBERNED)  Madrid Spain"},{"name":"Institut de Neuroci\u00e8ncies Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra O","family":"Morcillo\u2010Nieto","sequence":"additional","affiliation":[{"name":"Memory Unit, IR SANT PAU Hospital de la Santa Creu i Sant Pau  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Neurodegenerativas (CIBERNED)  Madrid Spain"},{"name":"Institut de Neuroci\u00e8ncies Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Serrano","sequence":"additional","affiliation":[{"name":"Memory Unit, IR SANT PAU Hospital de la Santa Creu i Sant Pau  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bessy","family":"Benejam","sequence":"additional","affiliation":[{"name":"Memory Unit, IR SANT PAU Hospital de la Santa Creu i Sant Pau  Barcelona Spain"},{"name":"Barcelona Down Medical Center Fundaci\u00f3 Catalana S\u00edndrome de Down  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Videla","sequence":"additional","affiliation":[{"name":"Memory Unit, IR SANT PAU Hospital de la Santa Creu i Sant Pau  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Neurodegenerativas (CIBERNED)  Madrid Spain"},{"name":"Barcelona Down Medical Center Fundaci\u00f3 Catalana S\u00edndrome de Down  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Barroeta","sequence":"additional","affiliation":[{"name":"Memory Unit, IR SANT PAU Hospital de la Santa Creu i Sant Pau  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Neurodegenerativas (CIBERNED)  Madrid Spain"},{"name":"Barcelona Down Medical Center Fundaci\u00f3 Catalana S\u00edndrome de Down  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Barcelona Down Medical Center Fundaci\u00f3 Catalana S\u00edndrome de Down  Barcelona 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