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The vermiform appendix impacts the risk of developing Parkinson's disease.

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 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 ?-synuclein. Together, we propose that the normal human appendix contains pathogenic forms of ?-synuclein that affect the risk of developing PD.

SUBMITTER: Killinger BA

PROVIDER: S-EPMC6319259 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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The vermiform appendix impacts the risk of developing Parkinson's disease.

Killinger Bryan A BA Madaj Zachary Z Sikora Jacek W JW Rey Nolwen N Haas Alec J AJ Vepa Yamini Y Lindqvist Daniel D Chen Honglei H Thomas Paul M PM Brundin Patrik P Brundin Lena L Labrie Viviane V

Science translational medicine 20181001 465

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 ...[more]

PMID: 30381408

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Project description:Cognitive decline is common in Parkinson's disease (PD), and precise cognitive assessment is important for diagnosis, prognosis, and treatment. To date, there are no studies in PD investigating cultural bias on neuropsychological tests. Clinical practice in multicultural societies such as, Toronto Canada where nearly half of the population is comprised of first generation immigrants, presents important challenges as most neuropsychological tools were developed in Anglosphere cultures (e.g., USA, UK) and normed in more homogeneous groups. We examine total scores and rates of deficits on tests of visuoperceptual/visuospatial, attention, memory, and executive functions in Canadians with PD born in Anglosphere countries (n = 248) vs. in Canadians with PD born in other regions (International group; n = 167). The International group shows lower scores and greater rates of deficits on all visuoperceptual and some executive function tasks, but not on attention or memory measures. These biases are not explained by demographic and clinical variables as groups were comparable. Age at immigration, years in Canada, and English proficiency also do not account for the observed biases. In contrast, group differences are strongly mediated by the Historical Index of Human Development of the participants' country of birth, which reflects economic, health, and educational potential of a country at the time of birth. In sum, our findings demonstrate lasting biases on neuropsychological tests despite significant exposure to, and participation in, Canadian culture. These biases are most striking on visuoperceptual measures and non-verbal executive tasks which many clinicians still considered to be "culture-fair" despite the growing evidence from the field of cross-cultural neuropsychology to the contrary. Our findings also illustrate that socio-development context captures important aspects of culture that relate to cognition, and have important implications for clinical practice.

Dataset Information

The vermiform appendix impacts the risk of developing Parkinson's disease.

Publications

The vermiform appendix impacts the risk of developing Parkinson's disease.

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