alpha-synuclein and Colonic-Neoplasms

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.

Topics: Adult; Aged; Aged, 80 and over; alpha-Synuclein; Biomarkers; Colon; Colonic Neoplasms; Female; Humans; Male; Middle Aged; Parkinson Disease; Phosphorylation; Prodromal Symptoms; Rectal Neoplasms

We aimed to compare immunoreactivity patterns of four different anti-α-syn antibodies in surgical specimens of the gastrointestinal tract of Parkinson disease and control cases. Surgical specimens from stomach, small and large bowel of 6 PD cases and 12 controls were studied. Primary antibodies: anti-α-syn clone KM51, anti-phosphorylated α-syn Ser129, anti-α-syn clone 15G7 and anti-nitrated α-syn505. We found different immunoreactivity patterns: (a) coarse, Lewy-body-like aggregates labelled by the 4 antibodies and detected in 4/6 PD cases and in 1/12 controls; (b) distinct punctate cytoplasmic staining of ganglion cells labelled by anti-phosphorylated-α-syn and detected in 3/6 PD cases and 3/12 controls; (c) fine diffuse, synaptic-type staining of neural structures labelled by anti-α-syn-15G7 and anti-nitrated-α-syn505 and detected in all subjects. We conclude that different specific and non-specific immunoreactivity patterns are detected in surgical specimens of gastrointestinal tract when using different anti-α-syn antibodies, as they recognize different epitopes and states of alpha-synuclein protein. Coarse aggregates in neural structures seem to be the most promising marker for the diagnosis of Lewy-body parkinsonism when evaluating abnormal α-syn in the gastrointestinal tract.

Topics: Adult; Aged; Aged, 80 and over; alpha-Synuclein; Biomarkers; Case-Control Studies; Colonic Neoplasms; Enteric Nervous System; Female; Gastrointestinal Tract; Humans; Inflammatory Bowel Diseases; Lewy Bodies; Male; Middle Aged; Myenteric Plexus; Parkinson Disease; Protein Aggregates; Young Adult