α-Synuclein in the colon and premotor markers of Parkinson disease in neurologically normal subjects.
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.
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. neuronet@catholic.ac.kr.
Joong-Seok
http://orcid.org/0000-0001-8087-7977
JS
Kim
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.
In-Seok
IS
Park
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.
Hyung-Eun
HE
Park
Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Su-Young
SY
Kim
Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Jung A
JA
Yun
Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Chan Kwon
CK
Jung
Department of Gastroenterology, Yonsei Tree of Life Internal Medicine Clinic, Seongnam, Gyeonggi, Republic of Korea.
Hye-Young
HY
Sung
Department of General Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Jin-Kwon
JK
Lee
Department of General Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Won-Kyung
WK
Kang
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D003106:Colon / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000175:diagnosis* / Q000378:metabolism; D010766:Phosphorylation; D062706:Prodromal Symptoms; D012004:Rectal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D051844:alpha-Synuclein / Q000378:metabolism*
D015415:Biomarkers; D051844:alpha-Synuclein
Colon; Parkinson’s disease; Premotor markers; α-Synuclein