Skin nerve a-synuclein deposits A biomarker for idiopathic Parkinson disease

Vincenzo Donadio, Alex Incensi, Valentina Leta, Maria Pia Giannoccaro, Cesa Scaglione, Paolo Martinelli, Sabina Capellari, Patrizia Avoni, Agostino Baruzzi, Rocco Liguori

Research output: Contribution to journalArticlepeer-review


Objective: To investigate (1) whether phosphorylated a-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 a-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 a-synuclein considered the pathologic form of a-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 a-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 a-synuclein in proximal peripheral nerves is a sensitive biomarker for IPD diagnosis, helping to differentiate IPD from other parkinsonisms. Neuritic inclusions of a-synuclein were correlated with a small-fiber neuropathy, suggesting their direct role in peripheral nerve fiber damage. Classification of evidence: This study provides Class III evidence that the presence of phosphorylated a-synuclein in skin nerve fibers on skin biopsy accurately distinguishes IPD from other forms of parkinsonism.

Original languageEnglish
Pages (from-to)1362-1369
Number of pages8
Issue number15
Publication statusPublished - Apr 15 2014

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)


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