Objective: To evaluate longitudinal consistency in the assessment of misfolded α-synuclein aggregates (syn-seeds) in cerebrospinal fluid (CSF) by α-synuclein seed amplification assay (synSAA).

Background: synSAA can detect minute levels of syn-seeds in CSF from manifest or prodromal individuals with underlying α-synuclein pathology. The Progression Parkinson’s Markers Initiative (PPMI) is a longitudinal study of participants with sporadic and genetic forms of Parkinson’s disease (PD), participants with prodromal features such as hyposmia or REM sleep behavior disorder (RBD), non-manifesting carries (NMC) of pathogenic variants associated to PD, and healthy controls (HC).

Method: CSF samples from PPMI participants have been analyzed over the last 4 years at Amprion using CSF_synSAA. Over this time, assay conditions were improved, and three distinct versions were released for research use (150h, 24h, and 35h CSF_synSAAs). The 150h synSAA had low sensitivity for Type2 syn-seeds found in multiple system atrophy (MSA), but all conditions were effective at amplifying Type 1 syn-seeds. Qualitative synSAA results were determined for each visit regardless of the assay condition used.  The analysis here included data collected up to January 5^th, 2026.

Results: CSF synSAA results were available for 4183 participants, including 1389 PD, 2471 prodromal, and 323 HC. 30% (1238) of cases had synSAA results from more than one visit, including 633 PD [444 sporadic PD, 189 genetic PD], 563 prodromal, and 42 HC. 94% (595) of PD cases had consistent results from 2 or more visits [93% sPD, 95% gPD]. Categorized by their initial result, consistent results were observed in 96% (474) of Type1 cases, 56% (5) of Type2 cases, and 92% (116) of negative cases. 97% (356) of sPD cases had consistent Type1 syn-seeds.  95% (537) of prodromal cases had consistent results. Per initial synSAA test, consistent results were observed in 99% (303) of Type1 cases and 95% (234) of negative cases. 86% (36) of the HC cases had consistent results. Per initial synSAA test, consistent results were observed in 89% (16) of Type1 cases and 87% (20) of negative cases.

Conclusion: Production of syn-seeds and their spreading into CSF is not transient, it is a stable aspect of neuronal synuclein disease (NSD). These results also show the reproducibility of the synSAA in detecting syn-seeds in NSD cases, even when using different assay conditions.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/longitudinal-%ce%b1-synuclein-seed-amplification-assay-analysis-of-ppmi-participants/