Diagnostic accuracy and predictors of alpha-synuclein accumulation in the gastrointestinal tract of Parkinson’s disease

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.