Phosphorylated α-synuclein deposits in sural nerve deriving from Schwann cells: A biomarker for Parkinson's disease

Introduction: Paresthesia is common in Parkinson's disease (PD) patients. We assumed that peripheral nerve might be implicated. This study aimed to investigate whether phosphorylated alpha-synuclein (pSNCA) pathology occurred in sural nerve fibers and to explore the underlying pathogenesis of paresthesia of lower limbs associated with PD. Methods: Clinical assessments and sural nerve biopsy were performed to evaluate clinical characteristics and the deposition of total alpha-synuclein (tSNCA) and pSNCA in biopsy pieces using immunochemistry methods on 16 PD patients and 15 controls. In addition, immunofluorescence staining was performed using certain antibodies to characterize the component of sural nerve and to localize the expression of pSNCA. Results: Deposition of pSNCA was found in 16/16 PD patients with a high positive percentage of 100% but in 0/15 controls, however, all biopsy pieces showed positive response to tSNCA immunohistological staining in nerve fibers. pSNCA was expressed mainly in Schwann cells but scarcely in axons, demonstrating a novel pattern of pSNCA expression in peripheral nervous system. Conclusion: Our findings suggest that peripheral somatic sensory nerve is also involved in SNCA pathology in PD. The search for pSNCA in sural nerve might serve as a novel biomarker for early diagnosis of PD and pSNCA in sural nerve may derive from Schwann cells rather than propagate retrograde along the primary sensory neurons from the central nervous system.