The diagnostic discrimination of cutaneous α-synuclein deposition in Parkinson disease

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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.


Twenty-eight participants with PD and 23 control participants were studied by skin biopsies at multiple sites, autonomic function testing, and disease-specific scales.


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.


The α-synuclein ratio provides a sensitive and specific diagnostic biomarker of PD even in patients without autonomic failure.

Classification of evidence:

This study provides Class III evidence that cutaneous α-synuclein deposition accurately identifies patients with PD.

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