α-Synuclein Deposition in Sympathetic Nerve Fibers in Genetic Forms of Parkinson's Disease

BACKGROUND: Cytoplasmic inclusions of α-synuclein in brainstem neurons are characteristic of idiopathic Parkinson’ disease. Parkinson’s disease also entails α-synuclein buildup in sympathetic nerves. Among genetic forms of Parkinson’s disease the relative extents of sympathetic intra-neuronal accumulation of α-synuclein have not been reported. OBJECTIVE: This cross-sectional observational study compared magnitudes of intra-neuronal deposition of α-synuclein in common and rare genetic forms of Parkinson’s disease. METHODS: α-Synuclein deposition was quantified by the α-synuclein-tyrosine hydroxylase colocalization index in C2 cervical skin biopsies from 65 subjects. These included 30 subjects with pathogenic mutations in SNCA (N=3), PRKN (biallelic [N=7] and monoallelic [N=3]), LRRK2 (N=7), GBA (N=7), or PARK7/DJ1 (biallelic [N=1] and monoallelic [N=2]). 25 of the mutation carriers had Parkinson’s disease and 5 did not. Data were also analyzed from 19 idiopathic Parkinson’s disease patients and 16 control participants. RESULTS: α-Synuclein deposition varied as a function of genotype (F=16.7, p