title: Skin nerve α-synuclein deposits: a biomarker for idiopathic Parkinson disease.
abstract: OBJECTIVE
  To investigate (1) whether phosphorylated α-synuclein deposits in skin nerve fibers might represent a useful biomarker for idiopathic Parkinson disease (IPD), and (2) the underlying pathogenesis of peripheral neuropathy associated with IPD.
  
  
  METHODS
  Twenty-one well-characterized patients with IPD were studied together with 20 patients with parkinsonisms assumed not to have α-synuclein deposits (PAR; 10 patients fulfilling clinical criteria for vascular parkinsonism, 6 for tauopathies, and 4 with parkin mutations) and 30 controls. Subjects underwent nerve conduction velocities from the leg to evaluate large nerve fibers and skin biopsy from proximal (i.e., cervical) and distal (i.e., thigh and distal leg) sites to study small nerve fibers and deposits of phosphorylated α-synuclein considered the pathologic form of α-synuclein.
  
  
  RESULTS
  Patients with IPD showed a small nerve fiber neuropathy prevalent in the leg with preserved large nerve fibers. PAR patients showed normal large and small nerve fibers. Phosphorylated α-synuclein was not found in any skin sample in PAR patients and controls, but it was found in all patients with IPD in the cervical skin site. Abnormal deposits were correlated with leg epidermal denervation.
  
  
  CONCLUSIONS
  The search for phosphorylated α-synuclein in proximal peripheral nerves is a sensitive biomarker for IPD diagnosis, helping to differentiate IPD from other parkinsonisms. Neuritic inclusions of α-synuclein were correlated with a small-fiber neuropathy, suggesting their direct role in peripheral nerve fiber damage.
  
  
  METHODS
  This study provides Class III evidence that the presence of phosphorylated α-synuclein in skin nerve fibers on skin biopsy accurately distinguishes IPD from other forms of parkinsonism.
authors.affiliation: From the IRCCS Istituto delle Scienze Neurologiche (V.D., A.I., V.L., M.P.G., C.S., S.C., P.A., A.B., R.L.), Bologna; and Dipartimento di Scienze Biomediche e Neuromotorie (V.L., M.P.G., P.M., S.C., P.A., R.L.), Università di Bologna, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Donadio
authors.forename: Alex
authors.initials: A
authors.lastname: Incensi
authors.forename: Valentina
authors.initials: V
authors.lastname: Leta
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Giannoccaro
authors.forename: Cesa
authors.initials: C
authors.lastname: Scaglione
authors.forename: Paolo
authors.initials: P
authors.lastname: Martinelli
authors.forename: Sabina
authors.initials: S
authors.lastname: Capellari
authors.forename: Patrizia
authors.initials: P
authors.lastname: Avoni
authors.forename: Agostino
authors.initials: A
authors.lastname: Baruzzi
authors.forename: Rocco
authors.initials: R
authors.lastname: Liguori
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D009412:Nerve Fibers / Q000378:metabolism* / Q000473:pathology; D010300:Parkinson Disease / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D012867:Skin / Q000294:innervation / Q000378:metabolism* / Q000473:pathology; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D051844:alpha-Synuclein