The vermiform appendix impacts the risk of developing Parkinson’s disease

Research output: Contribution to journalArticle

Abstract

The pathogenesis of Parkinson’s disease (PD) involves the accumulation of aggregated -synuclein, which has been suggested to begin in the gastrointestinal tract. Here, we determined the capacity of the appendix to modify PD risk and influence pathogenesis. In two independent epidemiological datasets, involving more than 1.6 million individuals and over 91 million person-years, we observed that removal of the appendix decades before PD onset was associated with a lower risk for PD, particularly for individuals living in rural areas, and delayed the age of PD onset. We also found that the healthy human appendix contained intraneuronal -synuclein aggregates and an abundance of PD pathology–associated -synuclein truncation products that are known to accumulate in Lewy bodies, the pathological hallmark of PD. Lysates of human appendix tissue induced the rapid cleavage and oligo-merization of full-length recombinant -synuclein. Together, we propose that the normal human appendix contains pathogenic forms of -synuclein that affect the risk of developing PD.

Details

Authors
  • Bryan A. Killinger
  • Zachary Madaj
  • Jacek W. Sikora
  • Nolwen Rey
  • Alec J. Haas
  • Yamini Vepa
  • Daniel Lindqvist
  • Honglei Chen
  • Paul M. Thomas
  • Patrik Brundin
  • Lena Brundin
  • Viviane Labrie
Organisations
External organisations
  • Van Andel Research Institute
  • Northwestern University
  • Skåne University Hospital
  • Michigan State University
  • Paris-Saclay Institute of Neuroscience
  • Centre for Addiction and Mental Health (CAMH)
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences
Original languageEnglish
Article numberaar5280
JournalScience Translational Medicine
Volume10
Issue number465
Publication statusPublished - 2018
Publication categoryResearch
Peer-reviewedYes