Objective: To investigate the feasibility of α-synuclein(α-Syn) pathology in enteric nervous system (ENS) as a diagnostic marker for Parkinson’s disease, and to clarify the distribution of α-Syn and its modifications in non-neurodegenerative intestinal tract.

Background: As one of the important pathological markers of Parkinson’s disease (PD), the α-Syn pathology of the ENS has received special attention due to its many characteristics such as accessible, representative, and possibly becoming the early prediction of PD. Studies have confirmed the early and sustained accumulation of α-Syn in the gastrointestinal tract of patients with PD. However,the pathological expression of α-Syn in ENS showed no significantly difference between patients with PD and normal controls, and is not directly related to non-motor symptoms of the digestive system.

Method: We obtained the full-thickness tissues of normal intestinal from 20 intestinal tumor patients. Immunohistochemistry staining with monoclonal α-Syn and phosphorylated α-Syn  to clarify the expression of α-Syn. Neurofilament and the serial sections are used to achieving co-localization with α-Syn. Semi-quantitative counting was used to evaluate the expression in the ENS while p-α-Syn and NF were assessed by counting the number of neurons at high magnification field (20×).

Results: Positive staining of α-Syn was detected in the whole layer of the intestine in patients with non-neurodegenerative diseases. This staining pattern was concentrated in the submucosa and myenteric plexus. Correlation analysis showed that there was no significant correlation between the distribution and age or tumor stage. While the expression of p-α-Syn was observed only in the submucosa and myenteric plexus, with age-dependent pattern indicating that this pathological change constantly accumulated with age. In addition, we found the degenerative changes of the ENS were related to the degree of malignancy.

Conclusion: In all, we found that deposits of α-syn in the ENS were already present in people with non-neurodegenerative disorders, and of particular with age-dependent expression of p-α-Syn in the submucosa and myenteric plexus. This finding provides the basis and support for assessing the reliability of gastrointestinal pathology as an auxiliary diagnosis for synucleinopathy including PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/age-dependent-expression-of-%ce%b1-synuclein-and-its-modification-in-non-neurodegenerative-intestinal-tract/