title: Skin nerve misfolded α-synuclein in pure autonomic failure and Parkinson disease.
abstract: OBJECTIVE
  To characterize the expression in skin nerves of native (n-syn) and misfolded phosphorylated (p-syn) α-synucleins in pure autonomic failure (PAF) and idiopathic Parkinson disease (IPD). The specific aims were to (1) define the importance of n-syn and p-syn as disease biomarkers and (2) ascertain differences in abnormal synuclein skin nerve deposits.
  
  
  METHODS
  We studied 30 patients, including 16 well-characterized IPD patients and 14 patients fulfilling PAF diagnostic criteria, and 15 age-matched controls. Subjects underwent skin biopsy from proximal (ie, cervical) and distal (ie, thigh and leg) sites to study small nerve fiber and intraneural n-syn and p-syn.
  
  
  RESULTS
  PAF and IPD showed length-dependent somatic and autonomic small fiber loss, more severely expressed in patients with higher p-syn load. n-syn was similarly expressed in both groups of patients and controls. By contrast, p-syn was not evident in any skin sample of controls but was found in all PAF and IPD patients, although with different skin innervation. In addition, abnormal α-synuclein deposits were found in all analyzed skin samples in PAF but in only 49% of samples with a higher positivity rate at the proximal site in IPD.
  
  
  CONCLUSIONS
  (1) Intraneural p-syn was a reliable in vivo marker of PAF and IPD; (2) neuritic p-syn inclusions differed in PAF and IPD, suggesting a different underlying pathogenesis; (3) when searching for abnormal p-syn deposits in skin nerves, the site of analysis is irrelevant in PAF but it is critical in IPD.
authors.affiliation: IRCCS Istituto delle Scienze Neurologiche, Bologna, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Donadio
authors.affiliation: IRCCS Istituto delle Scienze Neurologiche, Bologna, Italy.
authors.forename: Alex
authors.initials: A
authors.lastname: Incensi
authors.affiliation: IRCCS Istituto delle Scienze Neurologiche, Bologna, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Piccinini
authors.affiliation: IRCCS Istituto delle Scienze Neurologiche, Bologna, Italy.|Department of Biomedical and Neuromotor Science, University of Bologna, Bologna, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Cortelli
authors.affiliation: IRCCS Istituto delle Scienze Neurologiche, Bologna, Italy.|Department of Biomedical and Neuromotor Science, University of Bologna, Bologna, Italy.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Giannoccaro
authors.affiliation: IRCCS Istituto delle Scienze Neurologiche, Bologna, Italy.
authors.forename: Agostino
authors.initials: A
authors.lastname: Baruzzi
authors.affiliation: IRCCS Istituto delle Scienze Neurologiche, Bologna, Italy.|Department of Biomedical and Neuromotor Science, University of Bologna, Bologna, Italy.
authors.forename: Rocco
authors.initials: R
authors.lastname: Liguori
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism*; D010523:Peripheral Nervous System Diseases / Q000378:metabolism*; D057165:Proteostasis Deficiencies / Q000378:metabolism*; D054970:Pure Autonomic Failure / Q000378:metabolism*; D012867:Skin / Q000294:innervation / Q000378:metabolism*; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D051844:alpha-Synuclein