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

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.

Madaj, ZacharyVan Andel Research Institute (författare)
Sikora, Jacek W.Northwestern University (författare)
Rey, NolwenVan Andel Research Institute,Paris-Saclay Institute of Neuroscience(Swepub:lu)med-ner (författare)
Haas, Alec J.Van Andel Research Institute (författare)
Vepa, YaminiVan Andel Research Institute (författare)
Lindqvist, DanielLund University,Lunds universitet,Enheten för klinisk suicidforskning,Forskargrupper vid Lunds universitet,Unit for clinical suicide research,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-del (författare)
Chen, HongleiMichigan State University (författare)
Thomas, Paul M.Northwestern University (författare)
Brundin, PatrikVan Andel Research Institute(Swepub:lu)mphy-pbr (författare)
Brundin, LenaVan Andel Research Institute(Swepub:lu)mphy-lla (författare)
Labrie, VivianeVan Andel Research Institute,Centre for Addiction and Mental Health (CAMH) (författare)
Van Andel Research InstituteNorthwestern University (creator_code:org_t)

Ingår i:Science Translational Medicine: American Association for the Advancement of Science (AAAS)10:4651946-62341946-6242

Av författaren/redakt...: Killinger, Bryan ...; Madaj, Zachary; Sikora, Jacek W.; Rey, Nolwen; Haas, Alec J.; Vepa, Yamini; visa fler...; Lindqvist, Danie ...; Chen, Honglei; Thomas, Paul M.; Brundin, Patrik; Brundin, Lena; Labrie, Viviane; visa färre...

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