Shin Chaewon, Kim Seong-Ik, Park Sung-Hye, Kim Jong-Min, Lee Jee-Young, Chung Sun Ju, Kim Jae Woo, Ahn Tae-Beom, Park Kye Won, Shin Jung Hwan, Lee Chan Young, Lee Hyuk-Joon, Kong Seong-Ho, Suh Yun-Suhk, Kim Han-Joon, Yang Han-Kwang, Jeon Beomseok
Department of Neurology, Chungnam National University Sejong Hospital, Chungnam National University College of Medicine, 20, Bodeum 7-ro, Sejong-si, Republic of Korea.
Department of Pathology, College of Medicine, Seoul National University, 103 Daehak-ro, Jongno-gu, Seoul, Republic of Korea.
NPJ Parkinsons Dis. 2024 Aug 15;10(1):155. doi: 10.1038/s41531-024-00766-3.
The only characteristic of alpha-synuclein (AS) accumulation in the gastrointestinal (GI) tract of Parkinson's disease (PD) found in pathological studies is the "rostrocaudal gradient," which describes the more frequent presence of AS accumulation in the upper GI tract than in the lower GI tract. This study aimed to determine the diagnostic accuracy and identify predictors of AS accumulation in the GI tract of PD patients. The frequency of AS accumulation in the GI tract was compared between PD patients (N = 97) who underwent radical GI surgery for cancer and individually matched controls (N = 94). We evaluated AS accumulation in the neural structures using phosphorylated AS immunohistochemistry. A multivariable logistic regression analysis was conducted to determine the predictors of AS accumulation in the GI tract of PD patients. The frequency of AS accumulation was significantly higher in PD patients (75.3%) than in controls (8.5%, p-value < 0.001). The sensitivity and specificity of the full-layer evaluation were 75.3% and 91.5%, respectively. When the evaluation was confined to the mucosal/submucosal layer, the sensitivity and specificity were 46.9% and 94.7%, respectively. The rostrocaudal gradient of AS accumulation was found in PD patients. The duration from symptom onset to surgery was significantly longer in PD patients with AS accumulation (4.9 ± 4.9 years) than in PD patients without AS accumulation (1.8 ± 4.1 years, p-value = 0.005). Both disease duration and rostrocaudal gradient independently predicted the presence of AS accumulation in the GI tract of PD patients. Our study suggests PD-related AS accumulation in the GI tract follows a temporally increasing but spatially static progression pattern.
病理研究发现，帕金森病（PD）患者胃肠道（GI）中α-突触核蛋白（AS）积累的唯一特征是“头尾梯度”，即AS积累在上消化道比下消化道更常见。本研究旨在确定PD患者胃肠道中AS积累的诊断准确性并识别其预测因素。对因癌症接受根治性胃肠道手术的PD患者（N = 97）和个体匹配的对照组（N = 94）进行了胃肠道中AS积累频率的比较。我们使用磷酸化AS免疫组织化学评估神经结构中的AS积累情况。进行多变量逻辑回归分析以确定PD患者胃肠道中AS积累的预测因素。PD患者中AS积累的频率（75.3%）显著高于对照组（8.5%，p值<0.001）。全层评估的敏感性和特异性分别为75.3%和91.5%。当评估仅限于黏膜/黏膜下层时，敏感性和特异性分别为46.9%和94.7%。在PD患者中发现了AS积累的头尾梯度。有AS积累的PD患者从症状出现到手术的持续时间（4.9±4.9年）显著长于无AS积累的PD患者（1.8±4.1年，p值=0.005）。疾病持续时间和头尾梯度均独立预测了PD患者胃肠道中AS积累的存在。我们的研究表明，PD相关的胃肠道AS积累遵循时间上增加但空间上静态的进展模式。
