Category: Parkinson's Disease: Pathophysiology
Objective: To understand molecular heterogeneity among Parkinson’s disease (PD) patients, and controls based on α-synuclein seed amplification assay (SAA) results.
Background: α-synuclein seed amplification assay (SAA) has emerged as a crucial biomarker for underlying Lewy pathology. Previous studies have shown variations in the proportion of cases with positive α-synuclein SAA results depending on carrier status for genetic variants as well as clinical features of PD, particularly hyposmia.
Method: α-synuclein-SAA analysis of cerebrospinal fluid (CSF) was performed using previously described methods. We assessed the frequency of positive α-synuclein SAA results in PD participants including those with LRRK2, GBA, PRKN and SNCA genetic variants. We compared α-synuclein SAA results to olfactory testing across groups including healthy control (HC) and participants with clinical features of parkinsonism but with Scans Without Evidence of Dopaminergic Deficiency (SWEDDs).
Results: A total of 1,054 cases were included: 783 PD cases, 212 Healthy Controls (HC) and 59 SWEDDs. The PD group included 527 sporadic cases, 144 LRRK2 variant carriers including those with G2019S and R1441G variants, 66 GBA carriers, 6 PRKN carriers and 11 SNCA carriers. α-Synuclein SAA results were positive in the vast majority of sporadic PD (492/527; 93%), GBA PD (61/66; 92.4%) and SNCA PD (11/11; 100%). Assay results were positive less frequently in LRRK2 (91/144; 63.2%) and PRKN (2/6; 33%). Across all groups, hyposmia was strongly associated with a positive α-synuclein SAA result. This finding was also present in HC and SWEDD subjects. 30.8% (8/26) of hyposmic HCs showed a positive α-synuclein SAA compared to 3.3% (6/180) normosmic HCs. 30% (3/10) SWEDD participants with hyposmia had positive α-synuclein SAA results compared to 14.3% (7/49) among normosmic SWEDD participants.
Conclusion: There is substantial variability in α-synuclein SAA across PD groups defined by genetic variant carrier status. While the frequency of positive α-synuclein SAA results differs across subgroups, the co-occurrence of positive α-synuclein SAA and hyposmia is a consistent clinical-biomarker phenotype in all PD subgroups and extends to groups without clinical or physiological abnormalities.
To cite this abstract in AMA style:
A. Siderowf, L. Concha-Marambio, D. Lafontant, R. Alcalay, L. Chahine, T. Faroud, D. Galasko, K. Kieburt, K. Merchant, B. Mollenhauer, K. Poston, J. Seibyl, C. Tanner, T. Simuni, D. Weintraub, A. Videnovic, S. Choi, C. Caspell-Garcia, C. Coffey, M. Frasier, L. Oliveira, S. Hutten, T. Sherer, C. Soto, K. Marek. Assessment of variation in α-synuclein seed amplification assay results in the PPMI cohort: Association with hyposmia [abstract]. Mov Disord. 2023; 38 (suppl 1). https://www.mdsabstracts.org/abstract/assessment-of-variation-in-%ce%b1-synuclein-seed-amplification-assay-results-in-the-ppmi-cohort-association-with-hyposmia/. Accessed November 22, 2024.« Back to 2023 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/assessment-of-variation-in-%ce%b1-synuclein-seed-amplification-assay-results-in-the-ppmi-cohort-association-with-hyposmia/