Scientific publications
Small fiber neuropathy and phosphorylated alpha-synuclein in the skin of E46K-SNCA mutation carriers
Carmona-Abellan M (1), Gabilondo I (2), Murueta-Goyena A (3), Khurana V (4), Tijero B (5), Luquin MR (6), Acera M (1), Del Pino R (1), Gardeazabal J (7), Martínez-Valbuena I (6), Sanchez-Pernaute R (8), Gómez-Esteban JC (9)
BACKGROUND AND OBJECTIVE:
In 2004 we described the E46K mutation in alpha-synuclein gene (E46K-SNCA), a rare point mutation causing an aggressive Lewy body disease with early prominent non-motor features and small fiber denervation of myocardium.
Considering the potential interest of the skin as a target for the development of biomarkers in Parkinson's Disease (PD), in this work we aimed to evaluate structural and functional integrity of small autonomic nerve fibers and phosphorylated alpha-synuclein (p-synuclein) deposition in the skin of E46K-SNCA carriers as compared to those observed in parkin gene mutation (PARK2) carriers and healthy controls.
PATIENTS AND METHODS:
We studied 7 E46K-SNCA carriers (3 dementia with Lewy bodies, 2 pure autonomic failure, 1 PD and 1 asymptomatic), 2 PARK2 carriers and 2 healthy controls to quantify intraepidermal nerve fiber density and p-synuclein deposition with cervical skin punch biopsies (immunohistochemistry against anti PGP9.5/UCHL-1, TH and p-synuclein) and sudomotor function with electrochemical skin conductance (ESC) (SudoScan).
RESULTS:
All E46K-SNCA carriers had moderate to severe p-synuclein deposits and small fiber neurodegeneration in different epidermal and dermal structures including nerve fascicles and glands, especially in carriers with Pure Autonomic Failure, while p-synuclein aggregates where absent in healthy controls and in one of two PARK2 carriers. The severity of the latter skin abnormalities in E46K-SNCA were correlated with sudomotor dysfunction (lower ESC) in hands (p = 0.035).
INTERPRETATION:
These results together with our previous findings support the relevance of E46K-SNCA mutation as a suitable model to study small fiber neuropathy in Lewy body diseases.
CITATION Parkinsonism Relat Disord. 2019 Jun 5. pii: S1353-8020(19)30259-7. doi: 10.1016/j.parkreldis.2019.05.038
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