Cutaneous α-Synuclein Signatures in Patients With Multiple System Atrophy and Parkinson Disease
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VIEW CORRECTIONAbstract
Background and Objectives
Multiple system atrophy (MSA) is a progressive neurodegenerative disorder caused by the abnormal accumulation of α-synuclein in the nervous system. Clinical features include autonomic and motor dysfunction, which overlap with those of Parkinson disease (PD), particularly at early disease stages. There is an unmet need for accurate diagnostic and prognostic biomarkers for MSA and, specifically, a critical need to distinguish MSA from other synucleinopathies, particularly PD. The purpose of the study was to develop a unique cutaneous pathologic signature of phosphorylated α-synuclein that could distinguish patients with MSA from patients with PD and healthy controls.
Methods
We studied 31 patients with MSA and 54 patients with PD diagnosed according to current clinical consensus criteria. We also included 24 matched controls. All participants underwent neurologic examinations, autonomic testing, and skin biopsies at 3 locations. The density of intraepidermal, sudomotor, and pilomotor nerve fibers was measured. The deposition of phosphorylated α-synuclein was quantified. Results were compared with clinical rating assessments and autonomic function test results.
Results
Patients with PD had reduced nerve fiber densities compared with patients with MSA (p < 0.05, all fiber types). All patients with MSA and 51/54 with PD had evidence of phosphorylated α-synuclein in at least one skin biopsy. No phosphorylated α-synuclein was detected in controls. Patients with MSA had greater phosphorylated α-synuclein deposition (p < 0.0001) and more widespread peripheral distribution (p < 0.0001) than patients with PD. These results provided >90% sensitivity and specificity in distinguishing between the 2 disorders.
Discussion
α-synuclein is present in the peripheral autonomic nerves of patients with MSA and when combined with synuclein distribution accurately distinguishes MSA from PD.
Classification of Evidence
This study provides Class II evidence that measurement of phosphorylated α-synuclein in skin biopsies can differentiate patients with MSA from those with PD.
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© 2023 American Academy of Neurology.
Publication History
Received: March 9, 2022
Accepted: November 17, 2022
Published online: January 19, 2023
Published in print: April 11, 2023
Disclosure
C.H. Gibbons serves as a scientific advisor and has stock options in CND Life Sciences. R. Freeman serves as a scientific advisor and has stock options in CND Life Sciences. R. Freeman previously served on the board of directors for CND Life Sciences. The other authors report no relevant disclosures. Go to Neurology.org/N for full disclosures.
Study Funding
This work was supported by the National Institutes of Health (NIH U54 NS065736), the Langer Family Foundation (to R.F.), the MSA Coalition (to R.F.), and the University of Colorado Skin Disease Research Center (to DSK).
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