Skin nerve misfolded α-synuclein in pure autonomic failure and Parkinson disease.
Ann Neurol
; 79(2): 306-16, 2016 Feb.
Article
en En
| MEDLINE
| ID: mdl-26606657
ABSTRACT
OBJECTIVE:
To characterize the expression in skin nerves of native (n-syn) and misfolded phosphorylated (p-syn) α-synucleins in pure autonomic failure (PAF) and idiopathic Parkinson disease (IPD). The specific aims were to (1) define the importance of n-syn and p-syn as disease biomarkers and (2) ascertain differences in abnormal synuclein skin nerve deposits.METHODS:
We studied 30 patients, including 16 well-characterized IPD patients and 14 patients fulfilling PAF diagnostic criteria, and 15 age-matched controls. Subjects underwent skin biopsy from proximal (ie, cervical) and distal (ie, thigh and leg) sites to study small nerve fiber and intraneural n-syn and p-syn.RESULTS:
PAF and IPD showed length-dependent somatic and autonomic small fiber loss, more severely expressed in patients with higher p-syn load. n-syn was similarly expressed in both groups of patients and controls. By contrast, p-syn was not evident in any skin sample of controls but was found in all PAF and IPD patients, although with different skin innervation. In addition, abnormal α-synuclein deposits were found in all analyzed skin samples in PAF but in only 49% of samples with a higher positivity rate at the proximal site in IPD.INTERPRETATION:
(1) Intraneural p-syn was a reliable in vivo marker of PAF and IPD; (2) neuritic p-syn inclusions differed in PAF and IPD, suggesting a different underlying pathogenesis; (3) when searching for abnormal p-syn deposits in skin nerves, the site of analysis is irrelevant in PAF but it is critical in IPD.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedad de Parkinson
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Piel
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Enfermedades del Sistema Nervioso Periférico
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Alfa-Sinucleína
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Insuficiencia Autonómica Pura
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Deficiencias en la Proteostasis
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Fibras Nerviosas
Límite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Ann Neurol
Año:
2016
Tipo del documento:
Article
País de afiliación:
Italia