Abstract

This study aimed to test whether peripheral α-synuclein staining might be useful for pure autonomic failure (PAF) diagnosis helping to differentiate degenerative from acquired peripheral autonomic neuropathy. We studied 21 patients with chronic peripheral autonomic neuropathy. Twelve patients showed a specific cause of neuropathy (acquired autonomic neuropathy – AAN) whereas nine had no specific acquired causes fulfilling the diagnostic criteria for PAF. Fifteen matched healthy subjects served as controls. Subjects underwent skin biopsy from thigh and leg to study skin innervation and phosphorylated α-synuclein deposits in the peripheral axons. Somatic and autonomic skin innervations were significantly decreased in peripheral autonomic neuropathy patients compared to controls. No differences were found between AAN and PAF. The deposits of α-synuclein were not found in controls but served to distinguish acquired from degenerative autonomic peripheral neuropathy: all pure autonomic failure patients showed α-synuclein deposits in the postganglionic sympathetic adrenergic and cholinergic nerve fibers which were absent in acquired autonomic neuropathy patients. Our study demonstrated that a search for neuritic inclusions of phosphorylated α-synuclein in the skin sympathetic nerve fibers could provide a sensitive in vivo biomarker for degenerative peripheral autonomic neuropathy and may shed more light on the PAF pathogenesis.

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