Increased Accumulation of α‐Synuclein in Inflamed Appendices of Parkinson's Disease Patients

Abstract Background The accumulation of α‐synuclein (α‐Syn) aggregates that leads to the onset of Parkinson's disease (PD) has been postulated to begin in the gastrointestinal tract. The normal human appendix contains pathogenic forms of α‐Syn, and appendectomy has been reported to affect the incidence of PD. Objective This study investigated appendix abnormality in patients with PD. Methods We assessed appendix morphology in 100 patients with PD and 50 control subjects by multislice spiral computed tomography. We analyzed the clinical characteristics of patients with PD with diseased appendices, which was confirmed in seven patients by histopathological analysis. Results Chronic appendicitis‐like lesions were detected in 53% of patients with PD, but these were not associated with the duration of motor symptoms. Appendicitis‐like lesions, impaired olfaction, and rapid eye movement sleep behavior disorder were risk factors for PD. The following clinical symptoms could be used to identify patients with PD with appendicitis‐like lesions: first motor symptoms were bradykinesia/rigidity, onset of motor symptoms in the central axis or left limb, prodromal constipation, high ratio of Unified Parkinson's Disease Rating Scale Part III score to symptom duration, low Montreal Cognitive Assessment score, and high Epworth Sleepiness Scale score. The seven patients with PD who were diagnosed with chronic appendicitis underwent appendectomy, and histopathological analysis revealed structural changes associated with chronic appendicitis and α‐Syn aggregation. Conclusions These results indicate an association between chronic appendicitis‐like lesions and PD, and suggest that α‐Syn accumulation in the diseased appendix occurs in PD. © 2021 International Parkinson and Movement Disorder Society