-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 alpha-synucleinopathies, several methods to identify peripheral alpha-synuclein (alpha-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 alpha-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 alpha-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 alpha-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.