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Related Experiment Video

Updated: Apr 4, 2026

Sequential Extraction of Soluble and Insoluble Alpha-Synuclein from Parkinsonian Brains
09:27

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Published on: January 5, 2016

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Brain-Only Versus GI-Only Synucleinopathy: A Comprehensive Autopsy Study With Both IHC and SAA.

Christina D Orru1, Thomas G Beach2, Charles H Adler3

  • 1Laboratory of Neurological Infections and Immunity, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases (NIAID), Hamilton, MT.

Medrxiv : the Preprint Server for Health Sciences
|April 3, 2026
PubMed
Summary

Parkinson's disease pathology may start in the gut, but brain pathology is far more common. Gastrointestinal Lewy body pathology is linked to disease severity.

Keywords:
RT-QuICautopsyetiologygastrointestinalimmunohistochemistryperipheral nervous systemphosphorylated alpha-synuclein

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Area of Science:

  • Neuropathology
  • Gastroenterology
  • Neurodegenerative Diseases

Background:

  • Braak's hypothesis suggests Lewy body pathology (LBP) in Parkinson's disease (PD) may originate in the gastrointestinal (GI) tract and spread to the central nervous system (CNS).
  • Investigating the origin and prevalence of LBP is crucial for understanding PD pathogenesis.

Purpose of the Study:

  • To test Braak's hypothesis by comparing the prevalence of alpha-synuclein LBP in the GI tract versus the brain in Parkinson's disease (PD) and control subjects.
  • To assess the clinical correlation of GI tract LBP with PD symptoms.

Main Methods:

  • Utilized immunohistochemistry (IHC) and RT QuIC (alpha-synuclein seed amplification assay - SAA) to detect LBP.
  • Analyzed autopsy samples from 50 PD subjects and 128 elderly controls (including incidental LBP and no LBP groups).
  • Examined 10 GI tract sites and selected brain regions.

Main Results:

  • LBP restricted to the GI tract was rare (2 subjects), while brain-restricted LBP was more common (11 subjects, estimated 32 with further testing).
  • Brain-only LBP is estimated to be 16 times more prevalent than GI-only LBP.
  • The number of SAA-positive GI sites correlated significantly with UPDRS motor scores and GI-related autonomic dysfunction (e.g., constipation, bowel movement issues).

Conclusions:

  • The study provides evidence that while GI tract LBP can occur, brain LBP is significantly more common in PD.
  • GI tract LBP is associated with clinical disease severity, supporting a potential role in PD progression.
  • Further research on brain regions is needed to fully characterize LBP distribution.