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

Bárbara Fernandes Gomes; Carly M Farris; Yihua Ma; Luis Concha-Marambio; Russ Lebovitz; Bengt Nellgård; Keti Dalla; Julius Constantinescu; Radu Constantinescu; Johan Gobom; Ulf Andreasson; Henrik Zetterberg; Kaj Blennow

doi:10.1016/j.parkreldis.2023.105807

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

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

Affiliations

¹ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. Electronic address: barbara.fernandes.gomes@gu.se.
² R&D Unit, Amprion Inc., San Diego, CA, 92121, USA.
³ Department of Anesthesiology and Intensive Care, Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
⁴ Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden.
⁵ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
⁶ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK; UK Dementia Research Institute at UCL, London, UK; Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, 53792, USA.

PMID: 37591709
DOI: 10.1016/j.parkreldis.2023.105807

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.

MeSH terms

Humans
Multiple System Atrophy* / diagnosis
Parkinson Disease* / diagnosis
Parkinsonian Disorders* / diagnosis
Synucleinopathies*
Tauopathies*
alpha-Synuclein

Substances

alpha-Synuclein