Objective: The aim of our study was to assess α-synuclein (α-syn) staining using the 5G4 antibody in skin samples of patients with idiopathic REM Sleep Behavior Disorder (iRBD) and healthy controls (HCs).

Background: iRBD represensts the strongest individual predictor of prodromal Parkinson´s disease (pPD). Staining of pathological α-syn in tissue biopsies gains recognition as an emerging biomarker of PD (both manifest and prodromal). Skin biopsy is of a special interest due to its accessibility. 5G4 antibody, specific for the disease-associated form of α-syn, had already yielded promising results in differentiating manifest and prodromal PD from HCs in colonic mucosa [1]. We aimed to determine its sensitivity and specificity in skin samples of iRBD cases and HCs.

Method: Patients from PARCAS [2] and PDBIOM [3] cohorts were deeply phenotyped in regard to MDS research criteria for pPD [4]. Skin punch biopsies (3.5 mm in diameter) were obtained from 2 regions per patient: right forearm and abdomen. Presence of pathological α-syn aggregates (5G4), neurofilaments (SMI-31) and marker of neuroectoderm derivates (anti-S100) was assessed. Histopathological immunoreactivity was evaluated as published previously [1].

Results: 15 iRBD patients fulfilling MDS research pPD criteria (13 males, 2 females) and 10 HCs not meeting pPD criteria (4 males, 6 females) were included. In forearm skin samples, pathological 5G4-positive neuritic structures were present in 11/15 iRBD patients and 0/10 HCs, yielding sensitivity 73,3%, specificity 100%, positive predictive value (PPV) 100% and negative predictive value (NPV) 71,4% for distinguishing iRBD subjects from HCs. In abdominal skin samples, 11/15 iRBD patients and 2/10 HCs stained positive, leading to sensitivity 73,3%, specificity 80%, PPV 84,6% and NPV 66,7%. Taking both samples together, sensitivity reached 100%, specificity 80%, PPV 88,2% and NPV 100% (p<0.001).

Conclusion: 5G4 antibody as a suitable marker of pathological α-syn differentiates iRBD patients from HCs in skin samples with high sensitivity and specificity. Skin biopsies thus represent a more accessible and promising future biomarker of pPD.
Acknowledgements:
This work was supported by the Slovak Research and Development Agency under contract no. APVV-18-0547 and the Operational Programme Integrated Infrastructure, funded by the ERDF under no. ITMS2014+:313011V455.

References: [1] Skorvanek M, Gelpi E, Mechirova E, et al. α-Synuclein antibody 5G4 identifies manifest and prodromal Parkinson’s disease in colonic mucosa. Mov Disord 2018; 33: 1366-1368. doi:10.1002/mds.27380
[2] Skorvanek M, Ladomirjakova Z, Han V, et al. Prevalence of prodromal Parkinson’s disease as defined by MDS research criteria among elderly patients undergoing colonoscopy. J Parkinson Dis 2017; 7: 481-489.
[3] Kulcsarova K, Ventosa JR, Feketeova E, et al. Comparison in detection of prodromal Parkinson’s disease patients using original and updated MDS research criteria in two independent cohorts. Parkinsonism Relat Disord 2021; 87: 48-55.
[4] Heinzel S, Berg D, Gasser T, et al. Update of the MDS research criteria for prodromal Parkinson´s disease. Mov Disord 2019; 34: 1464-1470.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/anti-%ce%b1-synuclein-antibody-5g4-differentiates-idiopathic-rem-sleep-behavior-disorder-patients-from-healthy-controls-in-skin-biopsies/