The vermiform appendix impacts the risk of developing Parkinson’s disease
(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)
- author
- organization
- publishing date
- 2018
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Science Translational Medicine
- volume
- 10
- issue
- 465
- article number
- aar5280
- publisher
- American Association for the Advancement of Science (AAAS)
- external identifiers
-
- scopus:85055838515
- pmid:30381408
- 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
- 2024-09-18 06:15:56
@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>}}, 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}}, doi = {{10.1126/scitranslmed.aar5280}}, volume = {{10}}, year = {{2018}}, }