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Gut-related Immune Activation in Parkinson's Disease with Asian LRRK2 Risk Variants: Associations with Systemic Inflammation and Clinical Severity

Toh, T. S.; Ding, H. X.; Khairul Anuar, A. N.; Zulhaimi, N. S.; Hor, J. W.; Pang, Y. C.; Kong, I. X.; Zulkefli, J.; Tay, Y. W.; Lit, L. C.; Lim, S.-Y.; Tan, A. H.

2026-07-14 neurology
10.64898/2026.07.10.26357757 medRxiv
Show abstract

LRRK2 is implicated in Parkinson's disease (PD) microbiome-gut-brain axis. We compared plasma lipopolysaccharide-binding protein (LBP) and soluble CD14 (sCD14), markers of gut permeability and endotoxin exposure, in PD patients with/without LRRK2 p.G2385R and/or p.R1628P, and controls, and examined their associations with systemic inflammation and clinical severity. Neither marker differed between groups. Across PD patients, LBP correlated with higher IL-6, TNF- and worse motor function, while sCD14 correlated with higher IL-6, CCL5 and worse constipation. These findings highlight the clinical relevance of endotoxin-related immune signaling in PD, without LRRK2 risk variant-specific associations and identify LBP as an emerging marker of inflammatory burden.

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