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)

(1) Neurodegenerative Diseases Group, Biocruces Bizkaia Health Research Institute, Cruces-Barakaldo, Bizkaia, Spain.
(2) Neurodegenerative Diseases Group, Biocruces Bizkaia Health Research Institute, Cruces-Barakaldo, Bizkaia, Spain; Neurology Department, Cruces University Hospital, Cruces-Barakaldo, Bizkaia, Spain; Ikerbasque: The Basque Foundation for Science, Bilbao, Spain.
(3) Neurology Department, Cruces University Hospital, Cruces-Barakaldo, Bizkaia, Spain.
(4) Ann Romney Center for Neurologic Disease, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, USA.
(5) Neurodegenerative Diseases Group, Biocruces Bizkaia Health Research Institute, Cruces-Barakaldo, Bizkaia, Spain; Neurology Department, Cruces University Hospital, Cruces-Barakaldo, Bizkaia, Spain.
(6) Department of Neurology, Clínica Universitaria de Navarra, Universidad de Navarra, Pamplona, Spain.
(7) Dermatology Department, Cruces University Hospital, Cruces-Barakaldo, Bizkaia, Spain.
(8) Andalusian Initiative for Advanced Therapies, Junta de Andalusia, Seville, Spain.
(9) Neurodegenerative Diseases Group, Biocruces Bizkaia Health Research Institute, Cruces-Barakaldo, Bizkaia, Spain; Neurology Department, Cruces University Hospital, Cruces-Barakaldo, Bizkaia, Spain

Magazine: Parkinsonism Related Disorders

Date: Jun 5, 2019

Neurology [SP]

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

you maybe interested

WHAT TECHNOLOGY
DO WE USE?

The Clínica is the greater private hospital with technological equipment of Spain, all in a single center.

Imagen de un PET, tecnología de vanguardia en la Clínica Universidad de Navarra

OUR
PROFESSIONALS

The professionals of the Clínica perform continuous research and training, always to the benefit of the patient.

Imagen profesionales de la Clínica Universidad de Navarra

WHY CHOOSE
THE CLINICA?

Learn why we are different from other healthcare centers. Quality, speed, comfort and results.

Imagen del edificio de la Clínica Universidad de Navarra