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. 2025 Jan 2;11:1. doi: 10.1038/s41531-024-00865-1

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© The Author(s) 2025

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

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Fig. 1 — 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.