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Area of Science:

  • Neuroscience
  • Gastroenterology
  • Pathology

Background:

  • Gastrointestinal symptoms frequently precede Parkinson disease (PD) neurological signs.
  • The diagnostic value of GI biopsies for early PD detection is debated.
  • Alpha-synuclein (α-syn) deposition patterns in the GI tract are variable and require clarification.

Purpose of the Study:

  • To investigate if combining GI α-syn mRNA expression with immunohistochemistry enhances GI biopsy utility in PD diagnosis.
  • To analyze α-syn staining and mRNA levels in the enteric nervous system across different patient groups.

Main Methods:

  • Compared α-syn immunohistochemistry and mRNA levels in pediatric controls, adult controls, PD clinic patients, and confirmed PD cases.
  • Utilized quantitative polymerase chain reaction to assess α-syn mRNA expression.
  • Examined α-syn staining in the enteric nervous system of stomach, colon, esophagus, appendix, and small bowel.

Main Results:

  • Parkinson disease patients exhibited Lewy bodies (LB) and diffuse neuronal α-syn staining.
  • Diffuse α-syn positivity was observed in GI tissues of all control groups (elderly, children, young adults).
  • α-Syn mRNA levels were highest and most variable in PD patients, with regional differences in the GI tract.

Conclusions:

  • Alpha-synuclein is normally present in the enteric nervous system, with detectable mRNA in all individuals.
  • Elevated and variable α-syn mRNA levels are characteristic of PD.
  • The presence of Lewy bodies in the GI tract, rather than α-syn expression alone, is crucial for differentiating neurodegenerative disease from controls.