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. 2025 May;12(5):659-663.
doi: 10.1002/mdc3.14333. Epub 2025 Jan 16.

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

David S Goldstein  1 , Parvez Alam  2 , Patti Sullivan  1 , Courtney Holmes  1 , Janna Gelsomino  1 , Andrew G Hughson  2 , Byron Caughey  2
Affiliations

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

David S Goldstein et al. Mov Disord Clin Pract. 2025 May.

Abstract

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.

Keywords: Lewy; Parkinson; biomarker; cerebrospinal fluid; synuclein.

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