Dataset Information

Cervical skin denervation associates with alpha-synuclein aggregates in Parkinson disease.

ABSTRACT:

Objective

Autonomic nervous system is involved at the onset of Parkinson disease (PD), and alpha-synuclein (?-Syn) and its phosphorylated form (p-?Syn) have been detected in dermal autonomic nerve fibers of PD. We assessed disease specific conformation variant of ?-Syn immunoreactivity in cutaneous nerves and characterized skin denervation patterns in PD and atypical parkinsonism (AP).

Methods

We enrolled 49 subjects, 19 with PD, 17 age-matched healthy controls, and 13 with AP. The manifestations of disease were rated on clinical scales. Skin biopsies from ankle, thigh, and neck were analyzed by immunofluorescence for p-?Syn, 5G4 as a conformation specific antibody to pathogenic ?-Syn and PGP9.5 as axonal marker. Intraepidermal nerve fiber density was measured in all anatomical sites as marker of neurodegeneration. Thirteen of the 19 PD underwent a 1 year follow-up visit plus skin biopsies.

Results

PD subjects displayed more severe cervical skin denervation (P < 0.03), which correlated to disease duration and worsened between initial and follow-up examination (P < 0.001). p-?Syn and 5G4 were equally sensitive and specific for the diagnosis of PD (area under the ROC was 0.839 for p-?Syn and 0.886 for 5G4). PD and AP with possible alpha-synucleinopathies share the features of marked cervical denervation and the presence of 5G4. In contrast AP with possible tauopathies were normal.

Interpretation

Conformational specific forms of ?-Syn are detectable in skin biopsy by immunofluorescence in PD, with a promising diagnostic efficiency similar to p-?Syn. Cervical cutaneous denervation correlates with disease duration and increases over time standing out as a potential biomarker of PD progression.

SUBMITTER: Melli G

PROVIDER: S-EPMC6243385 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Publications

Cervical skin denervation associates with alpha-synuclein aggregates in Parkinson disease.

Melli Giorgia G Vacchi Elena E Biemmi Vanessa V Galati Salvatore S Staedler Claudio C Ambrosini Roberto R Kaelin-Lang Alain A

Annals of clinical and translational neurology 20181014 11

<h4>Objective</h4>Autonomic nervous system is involved at the onset of Parkinson disease (PD), and alpha-synuclein (<i>α</i>-Syn) and its phosphorylated form (p-<i>α</i>Syn) have been detected in dermal autonomic nerve fibers of PD. We assessed disease specific conformation variant of <i>α</i>-Syn immunoreactivity in cutaneous nerves and characterized skin denervation patterns in PD and atypical parkinsonism (AP).<h4>Methods</h4>We enrolled 49 subjects, 19 with PD, 17 age-matched healthy control ...[more]

PMID: 30480033

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Dataset Information

Cervical skin denervation associates with alpha-synuclein aggregates in Parkinson disease.

Objective

Methods

Results

Interpretation

Publications

Cervical skin denervation associates with alpha-synuclein aggregates in Parkinson disease.

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