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Clinical Progression in Alpha-Synuclein Positive LRRK2-PD and Sporadic Parkinson's Disease: A Longitudinal Analysis
Journal article   Open access   Peer reviewed

Clinical Progression in Alpha-Synuclein Positive LRRK2-PD and Sporadic Parkinson's Disease: A Longitudinal Analysis

Lucy A Morse, Seung Ho Choi, Caroline Gochanour, David-Erick Lafontant, Lana M Chahine, Kalpana M Merchant, Barbara Wendelberger, Tanya Simuni and Parkinson's Progression Markers Initiative
Movement disorders clinical practice (Hoboken, N.J.)
04/19/2026
DOI: 10.1002/mdc3.70640
PMID: 42003081
url
https://doi.org/10.1002/mdc3.70640View
Published (Version of record) Open Access

Abstract

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). We aimed to assess how LRRK2-PD with αSyn aggregates on SAA (S+ LRRK2-PD) compares to S+ sPD. 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. 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. Longitudinal clinical progression of S+ LRRK2-PD and sPD in the PPMI study is similar despite differences in baseline features.
 LRRK2‐PD alpha‐synuclein sporadic Parkinson's disease

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