Elevated Cerebrospinal Fluid α-Synuclein Seeding Activity Predicts Central Lewy Body Diseases

Background: Cerebrospinal fluid (CSF) α-synuclein seeding activity (SSA) via a seed amplification assay might predict central Lewy body diseases (LBD) in at-risk individuals. Objective: The aim was to assess CSF SSA in a prospective, longitudinal study. Methods: Participants self-reported risk factors were genetics, olfactory dysfunction, dream enactment behavior, orthostatic intolerance, or hypotension; individuals who had ≥3 confirmed risk factors underwent CSF sampling and were followed for up to 7.5 years. Participants who developed a central LBD (LBD+) were compared to those who did not. Quadruplicate SSA areas under the curve (AUC) were averaged. Results: Of 11 subjects with average AUCs above 500,000 units, 7 (64%) developed a central LBD compared to 1 of 20 (5%), with AUCs below the cutoff value (P = 0.0011 by log-rank test). Conversely, 7 of 8 (88%) LBD+ participants had elevated initial AUCs. Conclusions: Increased CSF SSA predicts central LBDs. Individuals who develop a central LBD have elevated initial SSA AUCs.