The vermiform appendix impacts the risk of developing Parkinson's disease
- PMID: 30381408
- PMCID: PMC6319259
- DOI: 10.1126/scitranslmed.aar5280
The vermiform appendix impacts the risk of developing Parkinson's disease
Abstract
The pathogenesis of Parkinson's disease (PD) involves the accumulation of aggregated α-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 α-synuclein aggregates and an abundance of PD pathology-associated α-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 oligomerization of full-length recombinant α-synuclein. Together, we propose that the normal human appendix contains pathogenic forms of α-synuclein that affect the risk of developing PD.
Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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Comment in
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The appendix and the risk of Parkinson's disease: Appended notes on correlation and causation.Mov Disord. 2019 Feb;34(2):199. doi: 10.1002/mds.27599. Epub 2018 Dec 30. Mov Disord. 2019. PMID: 30597616 No abstract available.
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