Joseph R. Winer, Melanie J. Plastini, America Romero, Hillary Vossler, Isha Sai, Divya Channappa, Carla Abdelnour, Marian Shahid, Edward N. Wilson, Hamilton Oh, Christina B. Young, Alexandra Trelle, Maya Yutsis, Sharon J. Sha, Veronica Ramirez, Ronald C. Taylor, Kyan Younes, Tony Wyss-Coray, Michael D. Greicius, Victor W. Henderson, Anthony D. Wagner, Kathleen L. Poston, Elizabeth C. Mormino
INTRODUCTION: α-Synuclein is the hallmark pathology of Parkinson's disease and dementia with Lewy bodies, described together as Lewy body disease (LBD). We investigated effects of α-syn biomarker positivity in clinically unimpaired (CU) individuals. METHODS: We assessed α-syn status (α-syn ±) in 269 CU individuals using a cerebrospinal fluid (CSF) seed amplification assay (SAA). Fifty-six participants with AD and 85 LBD spectrum participants were included for comparison. We compared α-syn SAA results with demographics, fluid biomarkers, cognitive performance, and clinical measures. RESULTS: α -Syn 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 α-syn-, α-syn+ CU individuals were older, showed lower synaptic integrity, performed worse on tests of executive function and working memory, and reported more LBD-related non-motor symptoms. DISCUSSION: Further work is needed to understand the timeline of neural and clinical changes in α-syn+ CU individuals and heterogeneity in disease progression.