Objective: This study aimed to investigate Alpha-synuclein (AS) accumulation in the gastrointestinal (GI) tract of patients with early-onset PD (EOPD).

Background: AS accumulation is found not only in the brain but also in peripheral tissues, including the GI tract. While many studies have investigated peripheral AS accumulation as a potential in vivo pathological biomarker for PD, data regarding EOPD remain scarce.

Method: Patients with EOPD (age at onset ≤ 50 years) who underwent radical GI surgery for cancer were recruited. For each patient, two full-depth slides from the histologically normal upper and lower margins of surgical specimens were analyzed. Immunohistochemistry was performed using antibodies against phosphorylated AS (pAS) to detect pathological aggregation and neurofilament to confirm neural localization.

Results: A total of 10 EOPD patients 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 4 patients (40%). AS accumulation was identified in 6 patients (60%). Notably, one patient confirmed to have a spinocerebellar ataxia type 6 (SCA6) mutation (CACNA CAG repeat 14/20) also exhibited AS accumulation in the stomach.

Conclusion: These findings demonstrate that a substantial proportion of patients with EOPD exhibit AS accumulation in the GI tract comparable to that observed in late-onset PD. Furthermore, the detection of AS accumulation in the stomach of a patient with SCA6 implies that SCA6-related parkinsonism may share a gut-brain axis-related pathophysiology similar to that of idiopathic PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/enteric-alpha-synuclein-pathology-in-early-onset-parkinsons-disease-and-an-incidental-case-in-spinocerebellar-ataxia-type-6/