Phosphorylated α-synuclein in skin nerve fibres differentiates Parkinson's disease from multiple system atrophy

Brain. 2015 Aug;138(Pt 8):2310-21. doi: 10.1093/brain/awv138. Epub 2015 May 27.


Deposition of phosphorylated SNCA (also known as α-synuclein) in cutaneous nerve fibres has been shown pre- and post-mortem in Parkinson's disease. Thus far, no pre-mortem studies investigating the presence of phosphorylated SNCA in skin sympathetic nerve fibres of multiple system atrophy, another synucleinopathy, have been conducted. In this in vivo study, skin from the ventral forearm of 10 patients with multiple system atrophy and 10 with Parkinson's disease, together with six control subjects with essential tremor, were examined by immunohistochemistry. Phosphorylated SNCA deposits in skin sympathetic nerve fibres and dermal nerve fibre density were assessed. All patients with Parkinson's disease expressed phosphorylated SNCA in sympathetic skin nerve fibres, correlating with an age-independent denervation of autonomic skin elements. In contrast, no phosphorylated SNCA was found in autonomic skin nerve fibres of patients with multiple system atrophy and essential tremor control subjects. These findings support that phosphorylated SNCA deposition is causative for nerve fibre degeneration in Parkinson's disease. Moreover, pre-mortem investigation of phosphorylated SNCA in cutaneous nerve fibres may prove a relevant and easily conductible diagnostic procedure to differentiate Parkinson's disease from multiple system atrophy.

Keywords: Parkinson's disease cellular mechanisms; Parkinson’s disease; multiple system atrophy; neurodegeneration biomarkers; synucleinopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Brain / pathology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multiple System Atrophy / metabolism*
  • Multiple System Atrophy / pathology
  • Nerve Degeneration / pathology
  • Nerve Fibers / metabolism
  • Nerve Fibers / pathology*
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology*
  • Phosphorylation
  • Skin / innervation*
  • alpha-Synuclein / metabolism*


  • SNCA protein, human
  • alpha-Synuclein