CSF LRRK2: A biomarker for slower autonomic dysfunction progression in sporadic Parkinson's disease

The pathophysiological biomarkers underlying the progression of autonomic dysfunction in Parkinson's disease (PD) are not fully understood. We conducted a cohort analysis of 116 sporadic PD patients to determine whether CSF concentrations of total LRRK2 protein and its phosphorylated substrate p-Rab10 predict the trajectories of SCOPA-AUT scores over five years. CSF LRRK2 and p-Rab10 were similarly elevated in sporadic PD and LRRK2 mutation carriers compared with controls. In linear mixed-effects models, higher baseline CSF LRRK2 levels were associated with attenuated annual SCOPA-AUT progression (Ln LRRK2 * time interaction: β = -0.714 points/year; p = 0.003), whereas the interaction between Ln p-Rab10 and time was not significant. These findings indicate that CSF LRRK2 may serve as a biomarker for the progression of autonomic dysfunction in sporadic PD.