title: The diagnostic discrimination of cutaneous α-synuclein deposition in Parkinson disease.
abstract: OBJECTIVE
  To determine the diagnostic discrimination of cutaneous α-synuclein deposition in individuals with Parkinson disease (PD) with and without autonomic dysfunction on autonomic testing, in early and late stages of the disease, and of short and long duration.
  
  
  METHODS
  Twenty-eight participants with PD and 23 control participants were studied by skin biopsies at multiple sites, autonomic function testing, and disease-specific scales.
  
  
  RESULTS
  Skin biopsies provide >90% sensitivity and >90% specificity to distinguish PD from control participants across all biopsies sites with quantification of either pilomotor or sudomotor α-synuclein deposition. All individuals with PD have significantly higher cutaneous α-synuclein deposition than control participants, even those individuals with PD and no evidence of autonomic dysfunction. Deposition of α-synuclein is most prominent in sympathetic adrenergic nerve fibers innervating the arrector pili muscles, but is also present in sudomotor (sympathetic cholinergic) nerve fibers. α-Synuclein is present even in the early stages of disease and disease of short duration. α-Synuclein ratios were higher in individuals with autonomic failure, with more advanced stages of disease and disease of longer duration.
  
  
  CONCLUSIONS
  The α-synuclein ratio provides a sensitive and specific diagnostic biomarker of PD even in patients without autonomic failure.
  
  
  METHODS
  This study provides Class III evidence that cutaneous α-synuclein deposition accurately identifies patients with PD.
authors.affiliation: From the Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. cgibbons@bidmc.harvard.edu.
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Gibbons
authors.affiliation: From the Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Garcia
authors.affiliation: From the Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Ningshan
authors.initials: N
authors.lastname: Wang
authors.affiliation: From the Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Ludy C
authors.initials: LC
authors.lastname: Shih
authors.affiliation: From the Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Roy
authors.initials: R
authors.lastname: Freeman
mesh_terms: D000368:Aged; D001342:Autonomic Nervous System Diseases / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000175:diagnosis* / Q000378:metabolism*; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D012867:Skin / Q000378:metabolism*; D013997:Time Factors; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D051844:alpha-Synuclein