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. 2025 Feb;40(2):305-314.
doi: 10.1002/mds.30085. Epub 2024 Dec 18.

Association between the Amplification Parameters of the α-Synuclein Seed Amplification Assay and Clinical and Genetic Subtypes of Parkinson's Disease

Piergiorgio Grillo  1   2   3 , Luis Concha-Marambio  4 , Antonio Pisani  2   3 , Giulietta Maria Riboldi  1 , Un Jung Kang  1   5
Affiliations

Association between the Amplification Parameters of the α-Synuclein Seed Amplification Assay and Clinical and Genetic Subtypes of Parkinson's Disease

Piergiorgio Grillo et al. Mov Disord. 2025 Feb.

Abstract

Background: α-Synuclein seed amplification assay on cerebrospinal fluid (CSF-αSyn-SAA) has shown high accuracy for Parkinson's disease (PD) diagnosis. The analysis of CSF-αSyn-SAA parameters may provide useful insight to dissect the heterogeneity of synucleinopathies.

Objective: To assess differences in CSF-αSyn-SAA amplification parameters in participants with PD stratified by rapid eye movement (REM) sleep behavior disorder (RBD), dysautonomia, GBA, and LRRK2 variants.

Methods: Clinical and CSF-αSyn-SAA data from the Parkinson's Progression Marker Initiative dataset were used. CSF-αSyn-SAA parameters included maximum fluorescence (Fmax), time to reach 50% of Fmax (T50), time to threshold (TTT), slope, and area under the curve (AUC). Sporadic PD (n = 371) was stratified according to RBD and dysautonomia (DysA) symptoms. Genetic PD included carriers of pathogenic variants of GBA (GBA-PD, n = 52) and LRRK2 (LRRK2-PD, n = 124) gene.

Results: CSF-αSyn-SAA was positive in 77% of LRRK2-PD, 92.3% of GBA-PD, and 93.8% of sporadic PD. The LRRK2-PD cohort showed longer T50 and TTT, and smaller AUC than GBA-PD (P = 0.029, P = 0.029, P = 0.016, respectively) and sporadic PD (P = 0.034, P = 0.033, P = 0.014, respectively). In the sporadic cohort, CSF-αSyn-SAA parameters were similar between PD with (n = 157) and without (n = 190) RBD, whereas participants with DysA (n = 193) presented shorter T50 (P = 0.026) and larger AUC (P = 0.029) than those without (n = 150).

Conclusion: CSF-αSyn-SAA parameters vary across genetic and non-genetic PD subtypes at the group level. These differences are mostly driven by the presence of LRRK2 variants and DysA. Significant overlaps in the amplification parameter values exist between groups and limit their use at the individual level. Further studies are necessary to understand the mechanisms of CSF-αSyn-SAA parameter differences. © 2024 International Parkinson and Movement Disorder Society.

Keywords: GBA1; LRRK2; Parkinson's disease; RBD; α‐synuclein seed amplification assay.

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Conflict of interest statement

Financial Disclosures of all authors (for the preceding 12 months)

Dr. Un Kang receives consulting compensation as a SAB member of Amprion, Inc.

Dr. Giulietta Riboldi: nothing to disclose.

Dr. Piergiorgio Grillo: nothing to disclose.

Dr. Antonio Pisani: nothing to disclose.

Dr. Luis Concha-Marambio is funded internally by Amprion and by the MJFF (grants MJFF-025017, MJFF-024735, MJFF-021233, MJFF-024261).

Financial disclosure/conflict of Interest related to research covered in this article:

Dr. Kang is on the Scientific Advisory Board of Amprion, Inc. Dr. Concha is an employee of Amprion, Inc.

Dr. Luis Concha-Marambio is an employee of Amprion and declares employee stock option ownership and invention of patents related to SAA assigned to Amprion (US11970520B2, US11959927B2, US20190353669A1, US20230084155A1, and US20210223268A1).

References

    1. Kang UJ, Boehme AK, Fairfoul G, Shahnawaz M, Ma TC, Hutten SJ, et al. Comparative study of cerebrospinal fluid α-synuclein seeding aggregation assays for diagnosis of Parkinson’s disease. Mov Disord [Internet]. 2019. Apr 1 [cited 2024 Jun 17];34(4):536–44. Available from: https://pubmed.ncbi.nlm.nih.gov/30840785/ - PMC - PubMed
    1. Russo MJ, Orru CD, Concha-Marambio L, Giaisi S, Groveman BR, Farris CM, et al. High diagnostic performance of independent alpha-synuclein seed amplification assays for detection of early Parkinson’s disease. Acta Neuropathol Commun [Internet]. 2021. Dec 1 [cited 2024 Jun 17];9(1):1–13. Available from: https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-021-012... - DOI - PMC - PubMed
    1. Bargar C, Wang W, Gunzler SA, LeFevre A, Wang Z, Lerner AJ, et al. Streamlined alpha-synuclein RT-QuIC assay for various biospecimens in Parkinson’s disease and dementia with Lewy bodies. Acta Neuropathol Commun [Internet]. 2021. Dec 1 [cited 2024 Jun 17];9(1):1–13. Available from: https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-021-011... - DOI - PMC - PubMed
    1. Fairfoul G, McGuire LI, Pal S, Ironside JW, Neumann J, Christie S, et al. Alpha-synuclein RT-QuIC in the CSF of patients with alpha-synucleinopathies. Ann Clin Transl Neurol [Internet]. 2016. Oct 1 [cited 2024 Jun 28];3(10):812–8. Available from: https://pubmed.ncbi.nlm.nih.gov/27752516/ - PMC - PubMed
    1. Saborio GP, Permanne B, Soto C. Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding. Nature 2001 411:6839 [Internet]. 2001. Jun 14 [cited 2024 Jun 28];411(6839):810–3. Available from: https://www.nature.com/articles/35081095 - PubMed

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