Acta Neuropathologica

, Volume 127, Issue 2, pp 235–241

Accumulation of α-synuclein in the bowel of patients in the pre-clinical phase of Parkinson’s disease

  • David Hilton
  • Madeleine Stephens
  • Leanne Kirk
  • Philip Edwards
  • Ross Potter
  • John Zajicek
  • Ellie Broughton
  • Hannah Hagan
  • Camille Carroll
Original Paper

DOI: 10.1007/s00401-013-1214-6

Cite this article as:
Hilton, D., Stephens, M., Kirk, L. et al. Acta Neuropathol (2014) 127: 235. doi:10.1007/s00401-013-1214-6

Abstract

Parkinson’s disease primarily affects the central nervous system, but autopsy and small patient studies have revealed autonomic nervous system pathology in most cases. We looked for α-synuclein pathology in routinely acquired biopsies from patients and matched controls. Immunocytochemistry was performed and assessed blind to the clinical diagnoses. One hundred and seventeen gastrointestinal tissue samples from 62 patients, and 161 samples from 161 controls, were examined. Twelve biopsies from seven patients showed accumulation of α-synuclein within mucosal and submucosal nerve fibres, and ganglia, which was more extensive with an antibody to phosphorylated, than with an antibody to non-phosphorylated, α-synuclein. These included gastric, duodenal and colonic biopsies, and were taken up to 8 years prior to the onset of motor symptoms. All patients with positive biopsies had early autonomic symptoms and all controls were negative. This large scale study demonstrates that accumulation of α-synuclein in the gastrointestinal tract is a highly specific finding that could be used to confirm a clinical diagnosis of Parkinson’s disease. We have shown that α-synuclein accumulation occurs prior to the onset of motor symptoms in the upper, as well as the lower gastrointestinal tract, remains present in serial biopsies until the onset of motor symptoms and is predominantly composed of phosphorylated α-synuclein. Accumulation of α-synuclein in the bowel therefore offers an accessible biomarker which allows further study of the early stages of the disease and could be of value in the assessment of disease modifying treatments.

Keywords

Parkinson’s disease Bowel α-synuclein Pre-clinical 

Supplementary material

401_2013_1214_MOESM1_ESM.doc (38 kb)
Supplementary material 1 (DOC 38 kb)
401_2013_1214_MOESM2_ESM.docx (54 kb)
Supplementary material 2 (DOCX 55 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • David Hilton
    • 1
  • Madeleine Stephens
    • 1
  • Leanne Kirk
    • 1
  • Philip Edwards
    • 1
  • Ross Potter
    • 1
  • John Zajicek
    • 2
  • Ellie Broughton
    • 3
  • Hannah Hagan
    • 3
  • Camille Carroll
    • 2
  1. 1.Department of Cellular and Anatomical PathologyDerriford HospitalPlymouthUK
  2. 2.Institute of Translational and Stratified MedicinePlymouth University Peninsula Schools of Medicine and DentistryPlymouthUK
  3. 3.Department of NeurologyDerriford HospitalPlymouthUK