α-synuclein antibody 5G4 identifies idiopathic REM-sleep behavior disorder in abdominal skin biopsies.

INTRODUCTION: Idiopathic REM-sleep behavior disorder (iRBD) is considered the most specific prodromal marker of Parkinson's disease (PD). With the need to improve early detection of prodromal α-synucleinopathies, several methods to identify peripheral α-synuclein (α-syn) pathology have been exploited in manifest and prodromal PD with varying diagnostic accuracy. Recently, a disease specific 5G4 antibody has been evaluated in skin biopsies of manifest PD patients. The aim of our study was to analyze the 5G4 α-syn immunoreactivity in skin biopsies of deeply phenotyped subjects with iRBD and controls. METHODS: The study cohort consisted of 28 patients with PD, 24 subjects with iRBD and 27 healthy controls, recruited from the CEGEMOD, PDBIOM and PARCAS cohorts. All subjects were deeply phenotyped and assessed for prodromal PD (pPD) probability based on MDS research criteria. Abdominal skin punch biopsies were processed and stained using a conformation specific 5G4 α-syn antibody as well as axonal markers SMI-31 and S100. RESULTS: 5G4-positivity was identified in 23/28 PD patients, 20/24 iRBD subjects and 8/27 healthy controls. Compared to healthy controls, sensitivity and specificity reached 83.33 % and 70.37 % for iRBD; and 82.14 % and 70.37 % for PD, respectively. 5G4-positivity rate in our study was irrespective of the calculated pPD probability of iRBD subjects. CONCLUSIONS: This work establishes the diagnostic yield of conformation specific 5G4 α-syn antibody testing in skin biopsies of subjects with pPD, specifically iRBD. The diagnostic accuracy for this method seems to be similar for both manifest and prodromal PD and is not dependent on the pPD probability ratios.

Influence of Escherichia coli infection on intestinal mucosal barrier integrity of germ-free piglets.

AIMS: We focused on investigating the influence of Escherichia coli (E. coli) on the intestinal barrier. MATERIAL AND METHODS: We studied changes in the distribution and secretory activities of goblet cells and enteroendocrine cells (EECs), as well as changes in the population of mast cells (MCs) in the jejunal and colonic mucosa of germ-free (GF) piglets as a healthy control group and GF piglets whose intestines were colonised with E. coli bacteria on day 5. KEY FINDINGS: The results suggest that the colon of GF piglets is more resistant and less prone to coliform bacterial infection compared to the jejunum. This can be confirmed by a lower degree of histopathological injury index as well as an improvement of the morphometric parameters of the colonic mucosa, together with a significantly increased (p < 0.05) expression of MUC1/EMA, and ZO-3. We also observed a significant decrease in the population of activated MCs (p < 0.001) and EECs (p < 0.001). These findings may indicate a rapid response and better preparation of the intestinal barrier for possible pathological attacks and the subsequent development of mucosal lesions during the development and progression of the intestinal diseases. SIGNIFICANCE: To date, gut-targeted therapeutic approaches that can modulate bacterial translocation and chronic inflammation are still in their infancy but represent one of the most promising areas of research for the development of new effective treatments or clinical strategies in the future. Therefore, a better understanding of these processes can significantly contribute to the development of these targeted strategies for disease prevention and treatment.