Enteric alpha-synuclein pathology in early-onset parkinsonism: Findings in a patient with SCA6

In Parkinson's disease (PD), alpha-synuclein (AS) accumulation is found not only in the brain but also in peripheral tissues, including the gastrointestinal (GI) tract. While many studies have investigated peripheral AS accumulation as a potential in vivo pathological biomarker for PD, data regarding early-onset PD and parkinsonism remain scarce. Therefore, this study aimed to investigate AS accumulation in the GI tract of patients with early-onset parkinsonism.

Patients with early-onset parkinsonism (age at onset ≤ 50 years) who underwent radical GI surgery for cancer were retrospectively identified. For each patient, two full-thickness tissue blocks from histologically normal proximal and distal resection margins were analyzed. Immunohistochemistry was performed using antibodies against phosphorylated AS (pAS) to detect pathological aggregation and neurofilament to confirm neural localization.

A total of 10 patients with early-onset parkinsonism were included in the analysis. The mean age at symptom onset was 43.2 ± 6.1 years. GI surgery was performed at a mean of 12.3 ± 9.0 years after disease onset. Genetic testing results were available for four patients (40%). AS accumulation was identified in 6 patients (60%). Notably, one patient confirmed to have a spinocerebellar ataxia type 6 (SCA6) mutation also exhibited AS accumulation in the stomach.

GI AS accumulation was observed in a substantial proportion of patients with early-onset parkinsonism. Furthermore, its presence in SCA6-related parkinsonism warrants further investigation of peripheral synuclein pathology in genetic parkinsonian disorders.