Objective: This study aimed to investigate the degree, distribution, and biochemical profile of phosphorylated α-synuclein (p-α-syn) in the peripheral nervous system of patients with SNCA duplication (PARK4).

Background: Lewy pathology is widely distributed in the central and peripheral nervous systems of patients with Parkinson’s disease (PD). However, few reports have described Lewy pathology in the peripheral nervous system of familial PD, including PARK4.

Method: Neuropathological examination, including immunohistochemistry for p-α-syn, was performed in an autopsy case with heterozygous duplication of the SNCA gene and five patients with PD. Frozen tissue from the sympathetic ganglia of patients was used for Western blotting.

Results: Postmortem neuropathological examination revealed widespread Lewy bodies from the brainstem to the neocortex, which were categorized as the diffuse neocortical type according to the DLB consensus guidelines in a patient with SNCA duplication. In the peripheral nervous system, p-α-syn-positive neuronal inclusions and neurites were more frequently visible in the sympathetic ganglion when compared with sporadic PD patients. Lewy pathology with denervation was observed in the sympathetic nerve of the left ventricular anterior wall. Furthermore, Lewy pathology revealed by immunohistochemistry for p-α-syn was visible in the myenteric plexus of the lower esophagus and nerve plexus in the adrenal gland more frequently than those of sporadic PD patients. Western blotting revealed a positive band at approximately 17 kDa, consistent with Lewy body disease in the sympathetic ganglion.

Conclusion: Lewy pathology is frequently observed in the peripheral nervous system of patients with the SNCA gene duplications. Western blotting results of the sympathetic ganglion were similar to those of the central nervous system.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/lewy-pathology-in-the-peripheral-nervous-system-of-snca-duplication/