Myelin damage in donor skin differentiates between synucleinopathies

Abstract Myelin alterations in the central nervous system have been reported in Parkinson’s disease (PD) and related neurodegenerative diseases, but little is known about the ultrastructure of the myelin-axon unit in the peripheral nervous system of subjects diseased with synucleinopathies. We here present an analysis of the myelin ultrastructure that characterize myelinated axons of nerve fiber bundles in cervical skin biopsies of 46 neuropathologically confirmed PD, DLB, MSA and non-neurological control post-mortem donors. We calculated a myelin damage score and classified over 1100 myelin sheaths by looking at myelin fragmentation and swellings with correlative light and electron microscopy. We found a higher load of myelin damage in the PD group compared to MSA and control groups. The observed structural abnormalities in the myelin sheaths may help to discriminate among subjects with synucleinopathies and control subjects and to understand the involvement of the peripheral innervation in the diseases. Our multiscale analysis of peripheral nerves highlights their potential as future classifiers for the detection and differentiation of synuclein diseases.