Clinical progression in alpha-synuclein positive LRRK2-PD and sporadic Parkinson’s disease: a longitudinal analysis

Abstract Background LRRK2-Parkinson’s disease (LRRK2-PD) is biologically heterogeneous with approximately 30% lacking aggregated alpha synuclein (αSyn) in cerebrospinal fluid by seed amplification assay (SAA). Prior work has suggested slower progression in LRRK2-PD compared to sporadic PD (sPD). Objective We aimed to assess how LRRK2-PD with αSyn aggregates on SAA (S+ LRRK2-PD) compares to S+ sPD. Methods Data from the Parkinson’s Progression Markers Initiative were used to compare S+ LRRK2-PD and S+ sPD cohorts propensity score-matched on age, disease duration, sex and levodopa equivalent dose (N = 79 per cohort). Baseline clinical and biological features and 4-year longitudinal features were assessed. Results At baseline, S+ LRRK2-PD participants had lower motor scores and dopaminergic deficit. Among measures showing within group progression, longitudinal trajectories did not differ significantly between groups. Conclusions Longitudinal clinical progression of S+ LRRK2-PD and sPD in the PPMI study is similar despite differences in baseline features.