α-Synuclein in cutaneous autonomic nerves

Neurology. 2013 Oct 29;81(18):1604-10. doi: 10.1212/WNL.0b013e3182a9f449. Epub 2013 Oct 2.

Abstract

Objective: To develop a cutaneous biomarker for Parkinson disease (PD).

Methods: 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.

Results: 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).

Conclusions: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • 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
  • alpha-Synuclein / metabolism*

Substances

  • alpha-Synuclein