OBJECTIVE: To characterize the expression in skin nerves of native (n- @entity15735 ) and misfolded phosphorylated (p- @entity15735 ) a-synucleins in @entity4728 ( @entity4728 ) and @entity191 ( @entity191 ). The specific aims were to: 1) define the importance of n- @entity15735 and p- @entity15735 as disease biomarkers; 2) ascertain differences in abnormal synuclein skin nerve deposits. MATERIALS AND METHODS: We studied 30 @entity1 including 16 well-characterized @entity191 and 14 @entity1 fulfilling @entity4728 diagnostic criteria and 15 age-matched controls. Subjects underwent skin biopsy from proximal (i.e. cervical) and distal (i.e. thigh and leg) sites to study small nerve fiber and intraneural n- @entity15735 and p- @entity15735 . RESULTS: @entity4728 and @entity191 showed a length-dependent somatic and autonomic small fiber loss, more severely expressed in @entity1 with higher p- @entity15735 load. N- @entity15735 was similarly expressed in both groups of @entity1 and controls. By contrast, p- @entity15735 was not evident in any skin sample of controls but was found in all @entity4728 and @entity191 @entity1 whilst with different skin innervation. In addition, abnormal a- @entity15735 deposits were found in all analyzed skin samples in @entity4728 but in only 49% of samples with a higher positivity rate in the proximal site in @entity191 . INTERPRETATION: 1) Intraneural p- @entity15735 was a reliable in vivo marker of @entity4728 and @entity191 ; 2) neuritic p- @entity15735 inclusions differed in @entity4728 and @entity191 suggesting a different underlying pathogenesis; 3) searching for abnormal p- @entity15735 deposits in skin nerves, the site of analysis is irrelevant in @entity4728 but it is critical in @entity191 . This article is protected by copyright. All rights reserved.

Skin nerve misfolded a-synuclein in pure XXXX .

@entity4728 :: ('MESH:D054970', 'Disease') :: ['pure autonomic failure', 'PAF'] @entity1 :: ('9606', 'Species') :: ['patients'] @entity15735 :: ('23336', 'Gene') :: ['syn'] @entity191 :: ('MESH:D010300', 'Disease') :: ['idiopathic Parkinson disease', 'IPD']
@entity191 :: (MESH:D010300,Disease) :: ['autonomic failure and Parkinson disease']
