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Skin nerve misfolded α‐synuclein in pure autonomic failure and P arkinson disease
Author(s) -
Donadio Vincenzo,
Incensi Alex,
Piccinini Cristina,
Cortelli Pietro,
Giannoccaro Maria Pia,
Baruzzi Agostino,
Liguori Rocco
Publication year - 2016
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.24567
Subject(s) - pure autonomic failure , pathogenesis , medicine , skin biopsy , pathology , biopsy , gastroenterology , blood pressure , orthostatic vital signs
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. Ann Neurol 2015 Ann Neurol 2016;79:306–316