Correlates of Zonulin and Claudin-5, markers of intestinal and brain endothelial permeability, in Parkinson's Disease: A pilot study

Abstract

IntroductionIdiopathic Parkinson's Disease is a chronic, progressive, neurodegenerative disease that affects the substantia nigra pars compacta and dopaminergic neurons in the brain stem. Since zonulin and claudin-5 are involved in intestinal and brain endothelial permeability and it is hypothesized that the brain-gut axis is relevant in IPD, the aim of our study is to evaluate whether the relationship between Zonulin and Claudin-5 levels and Parkinson's Disease patients. MethodsA total of 139 patients, including 34 mild, 33 moderate, 39 severe stage patients and 33 healthy controls were included. The patients’ demographic data, age of onset, disease duration, disease type and drugs were noted. UPDRS and H&Y scores were evaluated. Prodromal stage symptoms and non-motor symptoms were noted. Zonulin and Claudin-5 levels in the serum were studied. ResultsThe mean Zonulin value was significantly higher in the IPD group compared to the control one (16.0 ± 10.5 vs. 11.1 ± 4.3; p = 0.0012). Likewise, the mean Claudin-5 value in the IPD group was again significantly higher than in the control group (8.4 ± 5.5 vs. 6.2 ± 3.4; p = 0.0003). The combined ROC curve, though, showed only modest albeit significant discriminant ability. Moreover, neither zonulin nor claudin-5 related to age, phenotype or disease duration, and in terms of non-motor symptoms there was only a significant association between zonulin and urine problems and between claudin-5 and sleep symptoms. ConclusionOur results suggest an association of these markers of intestinal and brain endothelial permeability and IPD, although these remain modest and preliminary and warrant further consideration in larger studies including prodromal cases.