Objective: To assess correlations between cerebrospinal fluid (CSF) α-synuclein seed amplification assay (synSAA) and the phenoconversion rate, timing, and final diagnosis of idiopathic rapid eye movement sleep disorder (iRBD) patients.

Background: α-synuclein aggregates (syn-seeds) are found in the CSF of >90% of iRBD cases and phenoconversion to motor disorder is correlated with CSF_synSAA positivity. Clinopathological studies show that most iRBD cases present Lewy body (LB) pathology regardless of if they phenoconvert to Parkinson’s disease (PD) or dementia with LB (DLB). Conversely, clinical studies find that many iRBD cases progress to multiple system atrophy (MSA). Amprion’s synSAA differentiates two syn-seed types: Type1 and Type2 are associated with LB and glial cytoplasmic inclusion pathology, respectively.

Method: 86 subjects (26 iRBD, 60 healthy controls [HC]) underwent diagnostic lumbar puncture at Paracelsus-Elena Klinik. Diagnoses were finalized after comprehensive clinical evaluation and follow-up visits; iRBD was diagnosed through video polysomnography according to established criteria. CSF samples from the baseline visit (3 exceptions: 2 from visit 2, 1 from visit 3) were analyzed by synSAA at Amprion. Positive samples (synSAA+) with high (≥45,000RFU) and intermediate (≥3,000RFU & <45,000RFU) maximum fluorescence indicate Type1 and Type2 syn-seeds, respectively.

Results: Syn-seeds (100% Type1) were detected in 92.3% of iRBD cases. The time from symptoms to synSAA+ CSF ranged from 0.7 to 12.1 years. To date, 41.7% of synSAA+ iRBD cases have phenoconverted to a clinically diagnosed synucleinopathy; no synSAA- cases have phenoconverted. 60% and 40% of phenoconversions were to PD and DLB, respectively. The time from symptoms to phenoconversion ranged from 4.9 to 20.3 years; the time from baseline visit to phenoconversion ranged from 1.0 to 8.2 years. Specificity was 94.8% for HC cases.

Conclusion: Syn-seeds, exclusively Type1, were detected in most iRBD CSF samples, some of which were collected months after patients disclosed the first symptoms. Detection of Type1 syn-seeds in phenoconverters was consistent with final LB disease diagnoses and occurred up to 8.2 years before phenoconversion. synSAA can assist in understanding the underlying synuclein pathology in RBD cases and would distinguish between PD/DLB and a fatal neurodegenerative disease like MSA.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/identification-of-alpha-synuclein-pathology-in-idiopathic-rapid-eye-movement-sleep-disorder-participants-by-seed-amplification-assay/