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

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Purpose: 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. Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish
Pages (from-to)577-585
Number of pages9
JournalClinical Autonomic Research
Issue number6
Publication statusPublished - Dec 1 2019


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

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems
  • Clinical Neurology


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