Fig. 1: Study overview.

302 PD participants were assigned to the Discovery Cohort (n = 218, left panel) and Validation Cohort (n = 84, right panel). A Lasso-Cox regression was used to screen the best-performing marker out of 19 peripheral inflammation blood markers to predicate the duration of disability milestone-free survival. Next, with longitudinal data, LMEMs were used to correlate the annual change of this best-performing marker with disease progression as assessed by the annual change of H&Y stage and LED. Finally, we measured BBB permeability in the striatum and the level of α-synuclein in the blood to explore the potential mechanisms of the best-performing biomarker in promoting PD progression to milestones. BBB blood–brain barrier, H&Y Hoehn-Yahr, LED equivalent doses of levodopa, LMEMs linear mixed-effects models.