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α-Synuclein in the colon and premotor markers of Parkinson disease in neurologically normal subjects

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Abstract

Extranigral non-motor signs precede the first motor manifestations of Parkinson’s disease by many years in some patients. The presence of α-synuclein deposition within colon tissues in patients with Parkinson’s disease can aid in identifying early neuropathological changes prior to disease onset. In the present study, we evaluated the roles of non-motor symptoms and signs and imaging biomarkers of nigral neuronal changes and α-synuclein accumulation in the colon. Twelve subjects undergoing colectomy for primary colon cancer were recruited for this study. Immunohistochemical staining for α-synuclein in normal and phosphorylated forms was performed in normally appearing colonic tissue. We evaluated 16 candidate premotor risk factors in this study cohort. Among them, ten subjects showed positive immunostaining with normal- and phosphorylated-α-synuclein. An accumulation of premotor markers in each subject was accompanied with positive normal- and phosphorylated-α-synuclein immunostaining, ranging from 2 to 7 markers per subject, whereas the absence of Lewy bodies in the colon was associated with relative low numbers of premotor signs. A principal component analysis and a cluster analysis of these premotor markers suggest that urinary symptoms were commonly clustered with deposition of peripheral phosphorylated-α-synuclein. Among other premotor marker, color vision abnormalities were related to non-smoking. This mathematical approach confirmed the clustering of premotor markers in preclinical stage of Parkinson’s disease. This is the first report showing that α-synuclein in the colon and other premotor markers are related to each other in neurologically normal subjects.

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Acknowledgements

The authors wish to acknowledge the financial support of the Catholic Medical Center Research Foundation in the program year of 2013.

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Authors and Affiliations

  1. Department of Neurology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea

    Joong-Seok Kim, In-Seok Park & Hyung-Eun Park

  2. Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

    Su-Young Kim & Jung A Yun

  3. Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

    Chan Kwon Jung

  4. Department of Gastroenterology, Yonsei Tree of Life Internal Medicine Clinic, Seongnam, Gyeonggi, Republic of Korea

    Hye-Young Sung

  5. Department of General Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

    Jin-Kwon Lee & Won-Kyung Kang

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  1. Joong-Seok Kim
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Correspondence to Joong-Seok Kim.

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Kim, JS., Park, IS., Park, HE. et al. α-Synuclein in the colon and premotor markers of Parkinson disease in neurologically normal subjects. Neurol Sci 38, 171–179 (2017). https://doi.org/10.1007/s10072-016-2745-0

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  • DOI: https://doi.org/10.1007/s10072-016-2745-0

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