Skin sympathetic fiber α-synuclein deposits: a potential biomarker for pure autonomic failure

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 showing sympathetic and parasympathetic involvement as confirmed by cardiovascular reflexes and microneurography from the peroneal nerve. Twelve patients showed a specific cause of neuropathy (acquired autonomic neuropathy) whereas 9 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 patients with peripheral autonomic neuropathy compared to controls. No differences were found between acquired autonomic neuropathy and PAF. The deposits of α-synuclein were not found in controls but served to distinguish acquired from degenerative autonomic peripheral neuropathy: all patients with PAF showed α-synuclein deposits, which were absent in patients with acquired autonomic neuropathy. Colocalization study disclosed α-synuclein neuritic inclusions in the postganglionic sympathetic adrenergic and cholinergic nerve fibers.

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 pathogenesis of PAF.