Category: Parkinson's Disease: Genetics
Objective: We investigated positivity rate in dual GBA1+LRRK2-PD by comparing GBA1+LRRK2-PD carriers(n=13), GBA1-PD(n=169) and LRRK2-PD(n=175).
Background: GBA1 and LRRK2 variants represent the most common genetic risk factors for Parkinson’s disease (PD). Alpha-synuclein seed amplification assay (SAA), a reliable biomarker for synuclein pathology in PD, is positive in nearly all GBA1-PD and 2/3 of LRRK2-PD.
Method: A cross-sectional retrospective study of Parkinson’s Progression Markers Initiative (PPMI) data, assessing clinical features and SAA positivity amongst three genetic subgroups of PD participants.
Results: SAA positivity rate amongst GBA1+LRRK2-PD carriers(83%) is closer to GBA1-PD rate(87%) rather than LRRK2-PD rate(62%,p-value>0.05). GBA1+LRRK2-PD have both non-motor and motor phenotypic similarity to GBA1-PD,( p-value>0.05), including similar UPSIT percentile scores and MDS-UPDRS III(OFF) scores.
Conclusion: Dual GBA1+LRRK2-PD carriers are thought to have a milder, LRRK2-like phenotype, yet this PPMI cohort indicates that SAA positivity and phenotype are aligned with GBA1-PD. Larger cohorts with SAA data are required to confirm this observation.
Genetic subgroups and SAA positivity
To cite this abstract in AMA style:
P. Ponger, A. Nair, N. Johnson, C. Caspell-Garcia, D. Lafontant, R. Alcalay, P. Ppmi. SAA Positivity Rate Amongst Dual LRRK2-GBA1, GBA1 and LRRK2 Carriers with Parkinson’s Disease [abstract]. Mov Disord. 2026; 41 (suppl 1). https://www.mdsabstracts.org/abstract/saa-positivity-rate-amongst-dual-lrrk2-gba1-gba1-and-lrrk2-carriers-with-parkinsons-disease/. Accessed October 1, 2026.« Back to 2026 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/saa-positivity-rate-amongst-dual-lrrk2-gba1-gba1-and-lrrk2-carriers-with-parkinsons-disease/