Is alpha-synuclein in the colon a biomarker for premotor Parkinson's disease? Evidence from 3 cases

Mov Disord. 2012 May;27(6):716-9. doi: 10.1002/mds.25020. Epub 2012 May 1.


Background: Despite clinicopathological evidence that Parkinson's disease (PD) may begin in peripheral tissues, identification of premotor Parkinson's disease is not yet possible. Alpha-synuclein aggregation underlies Parkinson's disease pathology, and its presence in peripheral tissues may be a reliable disease biomarker.

Objective: We sought evidence of alpha-synuclein pathology in colonic tissues before the development of characteristic Parkinson's disease motor symptoms.

Methods: Old colon biopsy samples were available for three subjects with PD. Biopsies were obtained 2-5 years before PD onset. We performed immunohistochemistry studies for the presence of alpha-synuclein and Substance P in these samples.

Results: All subjects showed immunostaining for alpha-synuclein (two, five and two years before first motor Parkinson's disease symptom). No similar alpha-synuclein immunostaining was seen in 23 healthy controls. Staining of samples for substance P suggested colocalization of alpha-synuclein and substance P in perikarya and neurites.

Conclusions: This is the first demonstration of alpha-synuclein in colon tissue prior to onset of PD. Additional study is required to determine whether colonic mucosal biopsy may be a biomarker of premotor PD.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / metabolism
  • Colon / metabolism*
  • Colon / pathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neurites / metabolism
  • Neurites / pathology
  • Parkinson Disease / diagnosis*
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology
  • Substance P / metabolism
  • alpha-Synuclein / metabolism*


  • Biomarkers
  • alpha-Synuclein
  • Substance P