α-Synuclein Seed Amplification Assay Kinetic Measures Offer Diagnostic, Prognostic Value in PD
Assessing cerebrospinal fluid (CSF) α-synuclein seed amplification assay measures could help differentiate Parkinson disease (PD) from progressive supranuclear palsy with Lewy body co-pathology, according to study results published in The Lancet Neurology.
“Furthermore, faster seeding kinetics are found in GBA1-Parkinson disease and predict cognitive decline in Parkinson disease independently of Alzheimer disease co-pathology,” reported corresponding author Edwin Jabbari, PhD, of UCL Queen Square Institute of Neurology in London and coauthors.
The findings stemmed from a longitudinal study of participants with PD, progressive supranuclear palsy, and healthy controls from a trio of independent cohorts. Researchers analyzed CSF α-synuclein seed amplification assay measures and clinical data collected between 2005 and 2023 for a total 1631 participants.
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In the UK parkinsonism cohort, the α-synuclein seed amplification assay was positive in 96% of PD samples and 15% of progressive supranuclear palsy samples. Three-quarters of positive progressive supranuclear palsy samples had distinct low and slow seeding kinetics as a marker of Lewy body co-pathology, according to the study.
In the Parkinson's Progression Markers Initiative (PPMI) international observational study and the Tübingen Parkinson's disease cohorts, time to threshold (TTT) for a positive α-synuclein seed amplification assay result was faster in GBA1-associated PD compared with sporadic PD.
Over a median 4.5 years of follow-up, unfavorable outcomes occurred in 73% of patients from the PPMI cohort with α-synuclein seed amplification assay-positive PD.
In both the PPMI and Tübingen cohorts, baseline TTT predicted cognitive decline as a component of an unfavorable PD outcome: hazard ratios were 2.36 and 2.17 in the respective cohorts. In a subgroup of patients with PD without Alzheimer disease biomarkers, TTT again predicted cognitive decline (researchers reported a 1.80 hazard ratio).
“This suggests,” the authors wrote, “that fast TTT is a reflection of more aggressive α-synuclein seeding that increases the rate of Lewy body pathology spread to the cortex.”
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