The Presence of Alpha‐Synuclein in Skin from Melanoma and Patients with Parkinson's Disease

Background The misfolding and prion-like propagation of the protein alpha-synuclein (α-syn) is the leading molecular signature in Parkinson's disease (PD). There is a significant co-incidence of PD and melanoma which may suggest a shared pathophysiology. This study compared the presence of α-syn in neural crest-derived tissues, such as nevi, melanoma, skin tags and skin biopsies from PD cases and controls. Methods Biopsies from PD participants were obtained from patients of a tertiary referral center for dermatology and neurology in Mexico and a dermatopathology private center in Florida, USA, between January 2015 and March 2016. Biopsies from 7 patients with melanoma, 15 with nevi, 9 with skin tags, 8 with PD, and 9 skin biopsies from healthy volunteers were analyzed for immunohistochemical determination of α-syn and tyrosinase. All analyses were performed by pathologists blinded with respect to the clinical diagnosis. Results In healthy controls, α-syn immunopositivity was restricted to scattered cells in the basal layer of the epidermis and accounted for 1± 0.8% of the analyzed area. In PD patients, there was increased staining for α-syn PD (3.3 ± 2.3%), with a higher percentage of positive cells in nevi (7.7 ± 5.5%) and melanoma (13.6 ± 3.5%). There was no increased staining in skin tags compared to healthy controls. Conclusions Patients with PD and melanoma have increased staining for α-syn in their skin. We propose that neurons and melanocytes, both derived from neuroectodermal cells, may share protein synthesis and regulation pathways that become dysfunctional in PD and melanoma. This article is protected by copyright. All rights reserved.