Advanced

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

Killinger, Bryan A.; Madaj, Zachary; Sikora, Jacek W.; Rey, Nolwen LU ; Haas, Alec J.; Vepa, Yamini; Lindqvist, Daniel LU ; Chen, Honglei; Thomas, Paul M. and Brundin, Patrik LU , et al. (2018) In Science Translational Medicine 10(465).
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Science Translational Medicine
volume
10
issue
465
publisher
American Association for the Advancement of Science (AAAS)
external identifiers
  • scopus:85055838515
ISSN
1946-6234
DOI
10.1126/scitranslmed.aar5280
language
English
LU publication?
yes
id
34f2ed8e-a4da-42fb-a948-285a646bdc79
date added to LUP
2018-11-15 09:52:19
date last changed
2019-04-23 04:42:21
@article{34f2ed8e-a4da-42fb-a948-285a646bdc79,
  abstract     = {<p>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.</p>},
  articleno    = {aar5280},
  author       = {Killinger, Bryan A. and Madaj, Zachary and Sikora, Jacek W. and Rey, Nolwen and Haas, Alec J. and Vepa, Yamini and Lindqvist, Daniel and Chen, Honglei and Thomas, Paul M. and Brundin, Patrik and Brundin, Lena and Labrie, Viviane},
  issn         = {1946-6234},
  language     = {eng},
  number       = {465},
  publisher    = {American Association for the Advancement of Science (AAAS)},
  series       = {Science Translational Medicine},
  title        = {The vermiform appendix impacts the risk of developing Parkinson’s disease},
  url          = {http://dx.doi.org/10.1126/scitranslmed.aar5280},
  volume       = {10},
  year         = {2018},
}