Skin nerve α-synuclein deposits in Parkinson’s disease and other synucleinopathies: a review

  • Vincenzo DonadioEmail author
Review Article



The in vivo diagnosis of synucleinopathies is an important research aim since clinical diagnostic criteria show low accuracy. The skin innervation, especially the autonomic subdivision, is a useful region to search for abnormal α-syn aggregates in synucleinopathies since the peripheral sympathetic nerves can be the earliest-affected neural region and autonomic symptoms may precede the classical symptoms of these disorders.


The major advantages of skin biopsy as an in vivo diagnostic tool for synucleinopathies are that it is an inexpensive and easy-to-perform technique requiring only limited facilities, and that it is repeatable in long-term studies as it causes only minor discomfort to the patient.


This review analyzes current progress in this area of research that may facilitate the standardization of this method, potentially eliminating differences among laboratories in the implementation of the method.


The most suitable and commonly used technique for identifying in vivo α-syn aggregates in skin nerves is indirect immunofluorescence, although several aspects of this approach need to be standardized, particularly when synucleinopathies without autonomic failure present a patchy distribution of abnormal α-syn aggregates in skin nerves. By contrast, synucleinopathies with autonomic failure may present widespread diffusion of abnormal aggregates in autonomic skin nerves.


Phosphorylated α-synuclein Skin biopsy Pure autonomic failure Idiopathic Parkinson’s disease Dementia with Lewy bodies 


Compliance with ethical standards

Conflict of interest

There is no conflict of interest to report for this manuscript.


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© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.IRCCS Istituto Delle Scienze Neurologiche di Bologna (Italy)UOC Clinica NeurologicaBolognaItaly

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