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We investigated effects of \u03b1\u2010syn biomarker positivity in clinically unimpaired (CU) individuals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We assessed \u03b1\u2010syn status (\u03b1\u2010syn\u00a0\u00b1) in 269 CU individuals using a cerebrospinal fluid (CSF) seed amplification assay (SAA). Fifty\u2010six participants with AD and 85 LBD spectrum participants were included for comparison. We compared \u03b1\u2010syn SAA results with demographics, fluid biomarkers, cognitive performance, and clinical measures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\u03b1 \u2010Syn positivity was detected in 9% of CU individuals, a lower rate than in clinically impaired participants with AD (16%) and LBD diagnoses (81%). Compared to \u03b1\u2010syn\u2010, \u03b1\u2010syn+ CU individuals were older, showed lower synaptic integrity, performed worse on tests of executive function and working memory, and reported more LBD\u2010related non\u2010motor symptoms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Further work is needed to understand the timeline of neural and clinical changes in \u03b1\u2010syn+ CU individuals and heterogeneity in disease progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71455","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T03:17:16Z","timestamp":1777864636000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of \u03b1\u2010synuclein pathology on synaptic dysfunction and clinical outcomes in normal aging"],"prefix":"10.1002","volume":"22","author":[{"given":"Joseph R.","family":"Winer","sequence":"first","affiliation":[{"name":"Department of Neurology &amp; Neurological Sciences Stanford University School of Medicine  Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie J.","family":"Plastini","sequence":"additional","affiliation":[{"name":"Department of Neurology &amp; Neurological Sciences Stanford University School of Medicine  Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"America","family":"Romero","sequence":"additional","affiliation":[{"name":"Department of Neurology &amp; Neurological Sciences Stanford University School of Medicine  Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hillary","family":"Vossler","sequence":"additional","affiliation":[{"name":"Department of Neurology &amp; Neurological Sciences Stanford University School of Medicine  Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isha","family":"Sai","sequence":"additional","affiliation":[{"name":"Department of Neurology &amp; Neurological Sciences Stanford University School of Medicine  Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divya","family":"Channappa","sequence":"additional","affiliation":[{"name":"Department of Neurology &amp; Neurological Sciences Stanford University School of Medicine  Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Abdelnour","sequence":"additional","affiliation":[{"name":"Department of Neurology &amp; Neurological Sciences Stanford University School of Medicine  Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian","family":"Shahid\u2010Besanti","sequence":"additional","affiliation":[{"name":"Department of Neurology &amp; Neurological Sciences Stanford University School of Medicine  Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward N.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Neurology &amp; Neurological Sciences Stanford University School of Medicine  Palo Alto California USA"},{"name":"Wu Tsai Neurosciences Institute Stanford University  Stanford California USA"},{"name":"The Phil and Penny Knight Initiative for Brain Resilience Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamilton Se\u2010Hwee","family":"Oh","sequence":"additional","affiliation":[{"name":"Nash Family Department of Neuroscience Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Brain and Body Research Center of the Friedman Brain Institute Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Ronald M. 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