Category: Parkinson's Disease: Genetics
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.
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.
Method: α-Synuclein deposition was measured quantitatively as 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 PD and 5 did not. Data were also analyzed from 19 iPD patients and a control (CTRL) group consisting of 12 patients with unrelated diseases and 4 healthy volunteers.
Results: α-Synuclein-tyrosine hydroxylase colocalization indices varied as a function of genotype (F=16.7, p<0.0001). α-Synuclein deposition was above the control range in 100% of subjects with SNCA mutations, 100% with LRRK2 mutations, 95% with idiopathic Parkinson’s diease, 83% with GBA mutations, and 0% with biallelic PRKN mutations. The mean colocalization index in the biallelic PRKN group was significantly higher than in the CTRL group. Additionally, patients with biallelic PRKN mutations had higher colocalization indices than did their unaffected siblings.
Conclusion: Individuals with SNCA, DJ-1, LRRK2, or GBA mutations have substantial intra-neuronal α-syn deposition in sympathetic noradrenergic nerves in skin biopsies, whereas those with biallelic PRKN mutations do not. Biallelic PRKN patients may have mildly increased α-synuclein deposition compared to controls.
To cite this abstract in AMA style:
R. Isonaka, D. Goldstein, W. Zhu, E. Yoon, D. Ehrlich, A. Schindler, A. Kokkinis, M. Sabir, S. Scholz, S. Bandres-Ciga, C. Blauwendraat, P. Gonzalez-Alegre, G. Lopez, E. Sidransky, D. Narendra. α-Synuclein in sympathetic nerve fibers distinguishes PRKN from LRRK2 and other genetic forms of Parkinson’s Disease [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/%ce%b1-synuclein-in-sympathetic-nerve-fibers-distinguishes-prkn-from-lrrk2-and-other-genetic-forms-of-parkinsons-disease/. Accessed June 15, 2025.« Back to MDS Virtual Congress 2021
MDS Abstracts - https://www.mdsabstracts.org/abstract/%ce%b1-synuclein-in-sympathetic-nerve-fibers-distinguishes-prkn-from-lrrk2-and-other-genetic-forms-of-parkinsons-disease/