Diagnostic Value of Glycocalyx Shedding in Blood for Differentiating between Parkinson's Disease and Multiple System Atrophy.

BACKGROUND

Blood-brain barrier disruption is increasingly recognized in synucleinopathies, but the role of the endothelial glycocalyx (GLX) in Parkinson's disease (PD) and multiple system atrophy (MSA) remains unclear.

OBJECTIVES

The aim was to determine whether plasma GLX markers differ between PD, MSA, and healthy controls (HC), relate to clinical measures, and support differential diagnosis.

METHODS

Nine GLX analytes were quantified in plasma from 38 PD, 24 MSA, and 46 HC. Group differences were tested with multilinear regression including age and sex; associations with disease duration, Hoehn and Yahr stage, and Montreal Cognitive Assessment score were examined; gradient boosting classifiers plus Shapley Additive Explanations and univariate receiver operating characteristic (ROC) analyses evaluated discriminative performance.

RESULTS

PD showed reduced biglycan and cluster of differentiation 44 (CD44), whereas MSA showed increased chondroitin sulfate and reduced perlecan and CD44 versus comparators. Several GLX markers correlated with duration and cognition. Multianalyte GLX signatures classified groups with ROC area under curve, 0.79 to 0.88.

CONCLUSIONS

In this exploratory cohort, distinct GLX signatures reflect disease-specific neurovascular dysfunction and may aid stratification and monitoring. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.