α-Synuclein in cutaneous autonomic nerves

• Published in: Neurology Vol. 81; no. 18; p. 1604
• Main Authors: Wang, Ningshan, Gibbons, Christopher H, Lafo, Jacob, Freeman, Roy
• Format: Journal Article
• Language: English
• Published: United States 29.10.2013
• Subjects: Aged; alpha-Synuclein - metabolism; Autonomic Pathways - physiopathology; Case-Control Studies; Female; Heart Rate; Humans; Male; Middle Aged; Nerve Fibers - pathology; Nervous System Diseases - etiology; Neurologic Examination; Parkinson Disease - complications; Parkinson Disease - metabolism; Parkinson Disease - pathology; Posture - physiology; Respiration; Skin - innervation; Skin - pathology; Statistics as Topic
• ISSN: 1526-632X
• DOI: 10.1212/WNL.0b013e3182a9f449

To develop a cutaneous biomarker for Parkinson disease (PD). Twenty patients with PD and 14 age- and sex-matched control subjects underwent examinations, autonomic testing, and skin biopsies at the distal leg, distal thigh, and proximal thigh. α-Synuclein deposition and the density of intraepidermal, sudomotor, and pilomotor nerve fibers were measured. α-Synuclein deposition was normalized to nerve fiber density (the α-synuclein ratio). Results were compared with examination scores and autonomic function testing. Patients with PD had a distal sensory and autonomic neuropathy characterized by loss of intraepidermal and pilomotor fibers (p < 0.05 vs controls, all sites) and morphologic changes to sudomotor nerve fibers. Patients with PD had greater α-synuclein deposition and higher α-synuclein ratios compared with controls within pilomotor nerves and sudomotor nerves (p < 0.01, all sites) but not sensory nerves. Higher α-synuclein ratios correlated with Hoehn and Yahr scores (r = 0.58-0.71, p < 0.01), with sympathetic adrenergic function (r = -0.40 to -0.66, p < 0.01), and with parasympathetic function (r = -0.66 to -0.77, p > 0.01). We conclude that α-synuclein deposition is increased in cutaneous sympathetic adrenergic and sympathetic cholinergic fibers but not sensory fibers of patients with PD. Higher α-synuclein deposition is associated with greater autonomic dysfunction and more advanced PD. These data suggest that measures of α-synuclein deposition in cutaneous autonomic nerves may be a useful biomarker in patients with PD.