Understanding the role of appendix removal and risk for Parkinson’s
The takeawayThe appendix contains forms of alpha-synuclein that have the potential to become toxic to neurons. Appendectomy may be associated with a lower risk for Parkinson’s in rural-dwelling individuals and delay its onset.
Why is it important?It highlights the importance of improving our understanding of the role of the gut in Parkinson’s.
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Impact Opinion“This is a fascinating research report. And potentially a seminal paper, as it not only finds an association between the removal of the appendix and Parkinson’s (in people living in the rural environment at least), but also because it highlights the presence of misfolded alpha synuclein in the healthy appendix. And when extracted and administered to normal alpha synuclein, those misfolded versions of the protein cause the health proteins to misfold. Members of the Parkinson’s community need not rush out and order the removal of their appendices though. Firstly, this study has demonstrated an association, which does not necessarily indicate causation. In addtion, this study potentially provides support for numerous ongoing clinical trials exploring different methods of removing misfolded alpha synuclein in people with Parkinson’s, some of which are focused on the gut (such as the RASMET study).”
BackgroundThe appendix is a small, worm-like (hence “vermiform”) tube, found in the gut, protuding out at the point where the small intestine meets the colon. It contains immune cells and tissue involved in immune surveillance, as well as a whole range of bacteria. When it becomes inflamed, it is removed surgically in a procedure that is called an appendectomy.
Given its role in immune function, exposure to pathogens, and increasing evidence that misfolded alpha-synuclein – a major suspected pathological culprit in Parkinson’s – is also found in the gut, several studies have asked whether removal of the appendix affects the risk for Parkinson’s.
The detailsResearchers at the Van Andel Institute analysed data from two independent databases: the nationwide Swedish National Patient Registry (SNPR), which registers all diagnoses in the Swedish population, and the Parkinson’s Progression Markers Initiative (PPMI). They found that an appendectomy was associated with a 25% lower risk for Parkinson’s in Swedish, rural-dwelling individuals, although there was no effect in the portion of the population living in urban areas. They also found that an appendectomy was associated with later onset of Parkinson’s across both of these datasets.
The researchers also reported that abnormally folded alpha-synuclein could be found in tissue samples of appendices from 46 out of the 48 healthy individuals who were biopsied, ranging in age from younger than 20 to 84 years old. They also found that when extracts of this appendix tissue was mixed with normal alpha-synuclein, the normal version of the protein became abnormally misfolded into the conformation that damages neurons in Parkinson’s.
Next stepsThis is the latest of several studies in recent years, which have shown inconsistent results on the effects of appendectomy and risk for Parkinson’s. This study indicates a correlation, but does not prove there is a direct causal effect of appendectomy on Parkinson’s: it leaves open the possibility that a third, as yet unknown factor, could be increasing both the risk for appendix inflammation as well as Parkinson’s. More work is needed to understand the role of the gut and inflammation in the pathogenesis of Parkinson’s..
Where can I learn more?Marras, C., Lang, A. E., Austin, P. C., Lau, C., & Urbach, D. R. (2016). Appendectomy in mid and later life and risk of Parkinson’s disease: A population-based study. Mov Disord, 31(8), 1243-1247 – https://www.ncbi.nlm.nih.gov/pubmed/27241338
Palacios, N., Hughes, K. C., Cereda, E., Schwarzschild, M. A., & Ascherio, A. (2018). Appendectomy and risk of Parkinson’s disease in two large prospective cohorts of men and women. Mov Disord, 33(9), 1492-1496 – https://onlinelibrary.wiley.com/doi/abs/10.1002/mds.109
Svensson, E., Horvath-Puho, E., Stokholm, M. G., Sorensen, H. T., Henderson, V. W., & Borghammer, P. (2016). Appendectomy and risk of Parkinson’s disease: A nationwide cohort study with more than 10 years of follow-up. Mov Disord, 31(12), 1918-1922 – https://www.ncbi.nlm.nih.gov/pubmed/27621223