Objective: 1) To determine the possibility as a pathologic biomarker of alpha-synuclein (AS) accumulation in the gastrointestinal (GI) tract in patients with Parkinson’s disease (PD) and 2) to reveal pathological evidence of gut-to-brain or brain-to-gut progression of AS aggregates in large-scale, multicenter, and matched case-control design.

Background: Previous studies that attempted using AS accumulation in the GI tract for a pathologic biomarker of PD have shown various results. Recent evidence showed that the brain and the GI tract would have bi-directional relationship and transport of pathologic AS aggregates.

Method: Patients with PD were recruited from six tertiary hospitals. Controls were matched with age at operation, sex, and site of operation. All participants underwent radical GI surgery for cancer. Serial slides of the surgical specimens were stained by immunohistochemistry using phosphorylated AS (pAS) and neurofilament antibodies. The stained slides were anonymized and evaluated by experienced raters who were blinded to clinical information. The multi-variate logistic regression analysis was conducted to determine the impact of clinical characteristics on pAS positive rate.

Results: Total 355 pathologic blocks from 97 patients with PD and 94 matched controls were evaluated. pAS positivity was significantly higher in PD patients (75.3%) than in controls (8.5%, p-value<0.001). Sensitivity and specificity of full-layer evaluation were 75.3% and 91.5%, respectively. When evaluation was confined to mucosa-submucosal layers, sensntivity and specificity were 46.9% and 94.7%, respectively. Duration of symptom onset to operation was significantly longer in patients with pAS-positive slides (4.9±4.9 years) than in patients with pAS-negative (1.8±4.1 years, p-value=0.005). In the multi-variate logistic regressin analysis, both duration of symptom onset to opreation and operation site were independent predictor to the pAS positivity in PD.

Conclusion: The results confirmed that the conventional immunohistochemistry of the GI tract did not have sufficient diagnostic accuracy for a pathologic biomarker of PD. The significant temporal relationship of duration of symptom onset to operation and AS accumulation in the GI tract implies a consitent progression of Lewy pathology from the brain to the gut along with the disease course of PD.

References: Shin C, Park SH, Yun JY, Shin JH, Yang HK, Lee HJ, et al. Fundamental limit of alpha-synuclein pathology in gastrointestinal biopsy as a pathologic biomarker of Parkinson’s disease: Comparison with surgical specimens. Parkinsonism & related disorders. 2017;44:73-8.

Beach TG, Adler CH, Sue LI, Vedders L, Lue L, White Iii CL, et al. Multi-organ distribution of phosphorylated alpha-synuclein histopathology in subjects with Lewy body disorders. Acta neuropathologica. 2010;119(6):689-702.

Tsukita K, Sakamaki-Tsukita H, Tanaka K, Suenaga T, Takahashi R. Value of in vivo alpha-synuclein deposits in Parkinson’s disease: A systematic review and meta-analysis. Movement disorders : official journal of the Movement Disorder Society. 2019;34(10):1452-63.

« Back to 2023 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/a-multicenter-matched-case-control-study-of-alpha-synuclein-accumulation-in-the-gastrointestinal-tract-of-parkinsons-disease/