Consistent skin α-synuclein positivity in REM sleep behavior disorder - A two center two-to-four-year follow-up study

Parkinsonism Relat Disord. 2021 May:86:108-113. doi: 10.1016/j.parkreldis.2021.04.007. Epub 2021 Apr 17.

Abstract

Objective/methods: Phosphorylated alpha-synuclein (p-syn) in dermal nerves of patients with isolated REM sleep behavior disorder (iRBD) is detectable by immunofluorescence-labeling. Skin-biopsy-p-syn-positivity was recently postulated to be a prodromal marker of Parkinson's disease (PD) or related synucleinopathies. Here, we provide two-to four-year clinical and skin biopsy follow-up data of 33 iRBD patients, whose skin biopsy findings at baseline were reported in 2017.

Results: Follow-up biopsies were available from 25 patients (18 positive at baseline) and showed consistent findings over time in 24 patients. One patient converted from skin-biopsy-negativity to -positivity. P-syn-positivity was observed in iRBD patients who still had a normal FP-CIT-SPECT two years later. Clinically, five of the 23 at baseline skin-biopsy-positive patients (21.7%) had converted to PD or dementia with Lewy bodies at follow-up, but none of the skin-biopsy-negative patients.

Conclusions: Dermal p-syn in iRBD is most probably an early consistent marker of synucleinopathy and may support other indicators of conversion to manifest disease state.

Keywords: Alpha-synuclein; Dopamine transporter SPECT; Parkinson's disease; REM sleep Behavior disorder; Skin biopsy.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Lewy Body Disease / epidemiology
  • Male
  • Middle Aged
  • Parkinson Disease / epidemiology
  • Peripheral Nerves / pathology*
  • Prodromal Symptoms*
  • REM Sleep Behavior Disorder / pathology*
  • Skin / pathology*
  • alpha-Synuclein / metabolism*

Substances

  • SNCA protein, human
  • alpha-Synuclein