Gut-related Immune Activation in Parkinson’s Disease with Asian <i>LRRK2</i> Risk Variants: Associations with Systemic Inflammation and Clinical Severity

<jats:title>ABSTRACT</jats:title> <jats:p> <jats:italic>LRRK2</jats:italic> 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 <jats:italic>LRRK2</jats:italic> 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-α 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 <jats:italic>LRRK2</jats:italic> risk variant-specific associations and identify LBP as an emerging marker of inflammatory burden. </jats:p>