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. 2023 Dec:117:105807.
doi: 10.1016/j.parkreldis.2023.105807. Epub 2023 Aug 14.

α-Synuclein seed amplification assay as a diagnostic tool for parkinsonian disorders

Bárbara Fernandes Gomes  1 , Carly M Farris  2 , Yihua Ma  2 , Luis Concha-Marambio  2 , Russ Lebovitz  2 , Bengt Nellgård  3 , Keti Dalla  3 , Julius Constantinescu  4 , Radu Constantinescu  4 , Johan Gobom  5 , Ulf Andreasson  5 , Henrik Zetterberg  6 , Kaj Blennow  5
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Free article

α-Synuclein seed amplification assay as a diagnostic tool for parkinsonian disorders

Bárbara Fernandes Gomes et al. Parkinsonism Relat Disord. 2023 Dec.
Free article

Abstract

Introduction: Synucleinopathies such as Parkinson's disease (PD) and multiple system atrophy (MSA) can be challenging to diagnose due to the symptom overlap with, for example, atypical parkinsonisms like progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Seed amplification assays (SAA), developed for the detection of α-synuclein (αSyn) aggregates in CSF, have been successful when used as a biomarker evaluation for synucleinopathies. In this study, we investigated the potential of this assay to not only detect αSyn seeds in CSF, but also discriminate between movement disorders.

Methods: The αSyn-SAA was tested in a Scandinavian cohort composed of 129 CSF samples from patients with PD (n = 55), MSA (n = 27), CBD (n = 7), and PSP (n = 16), as well as healthy controls (HC, n = 24).

Results: The αSyn seed amplification assay (αSyn-SAA) was able to correctly identify all PD samples as positive (sensitivity of 100%) while also discriminating the PD group from HC (70.8% specificity, p < 0.0001) and tauopathies [CBD (71% specificity) and PSP (75% specificity), p < 0.0001)]. The αSyn-SAA was also able to identify almost all MSA samples as positive for αSyn aggregation (sensitivity of 92.6%). In general, this assay is able to discriminate between the synucleinopathies and tauopathies analyzed herein (p < 0.0001) despite the overlapping symptoms in these diseases.

Conclusion: These findings suggest the αSyn-SAA is a useful diagnostic tool for differentiating between different parkinsonian disorders, although further optimization may be needed.

Keywords: Alpha-synuclein; Atypical parkinsonian disorders; Biological assay; Biomarker; Parkinson's disease.

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Conflict of interest statement

Declaration of competing interest Potential conflicts of interest have been declared as follows: Co-author Henrik Zetterberg has served at scientific advisory boards and/or as a consultant for Abbvie, Alector, Annexon, Artery Therapeutics, AZTherapies, CogRx, Denali, Eisai, Nervgen, Novo Nordisk, Pinteon Therapeutics, Red Abbey Labs, Passage Bio, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, Biogen, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program. Co-author Kaj Blennow has served as a consultant, at advisory boards, or at data monitoring committees for Abcam, Axon, BioArctic, Biogen, JOMDD/Shimadzu. Julius Clinical, Lilly, MagQu, Novartis, Ono Pharma, Pharmatrophix, Prothena, Roche Diagnostics, and Siemens Healthineers, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program. Co-authors Luis Concha-Marambio, Carly M. Farris, Yihua Ma, and Russ Lebovitz are employees of Amprion, a biotechnology company that focuses on the commercial use of SAA (PMCA, RT-QuIC) for diagnostic purposes. They are also inventors in several patents associated to SAAs.

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