Background. Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor and nonmotor impairments, including constipation. Lewy bodies and neurites, the pathological hallmarks of PD, are found in the enteric nervous system (ENS) as well as the central nervous system. Constipation is a well-documented premotor symptom in PD, and recent reports have demonstrated Lewy pathology in gastrointestinal (GI) tissues of PD patients prior to the onset of motor symptoms. Objective. In the present study, we assessed Lewy pathology in the GI tracts of seven PD patients who had undergone a gastrectomy, gastric polypectomy, or colonic polypectomy prior to the onset of motor symptoms in order to assess whether the presence of pathological αSyn in the ENS could be a predictor for PD. Methods. GI tissue samples were collected from control patients and patients with premotor PD. Immunohistochemistry was performed using primary antibodies against α-synuclein (αSyn) and phosphorylated αSyn (pαSyn), after which Lewy pathology in each sample was assessed. Results. In all control and premotor PD patients, accumulation of αSyn was observed in the myenteric plexus in both the stomach and colon. In 82% (18/22) of control patients, mild-to-moderate accumulation of αSyn was observed in the submucosal plexus. However, there was no deposition of pαSyn in the ENS of control patients. In patients with premotor PD, abundant accumulation of αSyn was observed in the myenteric plexus, similar to control patients. On the other hand, pαSyn-positive aggregates were also observed in the nerve fibers in the muscularis propria in all examined patients with premotor PD (100%, 3/3), while the deposition of pαSyn in the submucosal plexus was only observed in one patient (14%, 1/7). Conclusion. Our results suggest that the detection of pαSyn, but not αSyn, especially in the muscularis propria of GI tracts, could be a sensitive prodromal biomarker for PD.

中文翻译：

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胃肠道固有肌中磷酸化 α-突触核蛋白的检测是帕金森病的敏感预测指标

背景。帕金森病 (PD) 是一种以运动和非运动障碍为特征的神经退行性疾病，包括便秘。路易体和神经突是 PD 的病理标志，存在于肠神经系统 (ENS) 和中枢神经系统中。便秘是 PD 中一个有据可查的运动前症状，最近的报告表明，在运动症状发作之前，PD 患者的胃肠道 (GI) 组织中存在路易病理学。客观。在本研究中，我们评估了 7 名 PD 患者在出现运动症状之前接受了胃切除术、胃息肉切除术或结肠息肉切除术的胃肠道路易病理学，以评估是否存在病理性αENS 中的 Syn 可能是 PD 的预测因子。方法。从对照患者和运动前 PD 患者收集 GI 组织样本。使用针对α-突触核蛋白 ( α Syn) 和磷酸化α Syn (p α Syn) 的一抗进行免疫组织化学，然后评估每个样品中的路易病理学。结果。在所有对照和运动前 PD 患者中，在胃和结肠的肌间神经丛中都观察到了α Syn 的积累。在 82% (18/22) 的对照患者中，在粘膜下丛中观察到轻度至中度的α Syn 积累。然而，没有沉积 p αSyn 在对照患者的 ENS 中。在运动前 PD 患者中，在肌间神经丛中观察到大量的α Syn 积累，与对照患者相似。另一方面，在所有检查的运动前 PD 患者（100%，3/3）的固有肌层神经纤维中也观察到p α Syn 阳性聚集物，而黏膜下丛中p α Syn 的沉积是仅在一名患者中观察到（14%，1/7）。结论。我们的结果表明，p α Syn 的检测，而不是α Syn 的检测，特别是在胃肠道固有肌层中，可能是 PD 的敏感前驱生物标志物。