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Elevated Cerebrospinal Fluid α-Synuclein Seeding Activity Predicts Central Lewy Body Diseases
David S Goldstein1, Parvez Alam2, Patti Sullivan1
1Autonomic Medicine Section (AMS), Clinical Neurosciences Program (CNP), Division of Intramural Research (DIR), National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, Maryland, USA.
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.
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