Distinctive distribution of phospho-alpha-synuclein in dermal nerves in multiple system atrophy

Mov Disord. 2015 Oct;30(12):1688-92. doi: 10.1002/mds.26293. Epub 2015 Jul 14.

Abstract

Background: MSA is characterized by deposition of alpha-synuclein (α-Syn) in oligodendrocytes and central nervous system (CNS) neurons. After recently detecting phospho-α-Syn (p-α-Syn) in dermal nerve fibers of patients with Parkinson's disease (PD), we assessed skin biopsies from patients with MSA to evaluate its potential role as a biomarker.

Methods: Skin biopsies of patients with MSA (n = 12), idiopathic PD (n = 30), tauopathies (n = 15), and normal controls (n = 39) were analyzed. P-α-Syn within dermal nerves was detected by immunofluorescence staining.

Results: p-α-Syn was found in 67% of patients with MSA and Parkinson's disease, but not in patients with tauopathy or controls when analyzing 15 consecutive sections. Sensitivity could be increased to 75% and 73%, respectively, by analyzing serial sections. In contrast to PD, where p-α-Syn clustered in autonomic fibers, deposits were mainly found in unmyelinated somatosensory fibers in MSA.

Conclusion: α-Syn pathology in MSA is not restricted to the CNS, and skin biopsy may be useful for the premortem study of p-α-Syn.

Keywords: Parkinson's disease; multiple system atrophy; phospho-alpha-synuclein; skin biopsy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biopsy
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multiple System Atrophy / pathology*
  • Nerve Fibers / metabolism*
  • Nerve Fibers / pathology
  • Parkinson Disease / pathology
  • Skin / innervation
  • Skin / pathology*
  • Ubiquitin Thiolesterase / metabolism
  • alpha-Synuclein / metabolism*

Substances

  • UCHL1 protein, human
  • alpha-Synuclein
  • Ubiquitin Thiolesterase