{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T10:20:24Z","timestamp":1789899624370,"version":"4.0.1"},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,12,29]],"date-time":"2015-12-29T00:00:00Z","timestamp":1451347200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To characterize the expression in skin nerves of native (n\u2010syn) and misfolded phosphorylated (p\u2010syn) \u03b1\u2010synucleins in pure autonomic failure (PAF) and idiopathic Parkinson disease (IPD). The specific aims were to (1) define the importance of n\u2010syn and p\u2010syn as disease biomarkers and (2) ascertain differences in abnormal synuclein skin nerve deposits.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We studied 30 patients, including 16 well\u2010characterized IPD patients and 14 patients fulfilling PAF diagnostic criteria, and 15 age\u2010matched controls. Subjects underwent skin biopsy from proximal (ie, cervical) and distal (ie, thigh and leg) sites to study small nerve fiber and intraneural n\u2010syn and p\u2010syn.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PAF and IPD showed length\u2010dependent somatic and autonomic small fiber loss, more severely expressed in patients with higher p\u2010syn load. n\u2010syn was similarly expressed in both groups of patients and controls. By contrast, p\u2010syn 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 \u03b1\u2010synuclein 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>(1) Intraneural p\u2010syn was a reliable in vivo marker of PAF and IPD; (2) neuritic p\u2010syn inclusions differed in PAF and IPD, suggesting a different underlying pathogenesis; (3) when searching for abnormal p\u2010syn 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\u2013316<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.24567","type":"journal-article","created":{"date-parts":[[2015,11,25]],"date-time":"2015-11-25T23:24:52Z","timestamp":1448493892000},"page":"306-316","source":"Crossref","is-referenced-by-count":146,"title":["Skin nerve misfolded \u03b1\u2010synuclein in pure autonomic failure and <scp>P<\/scp>arkinson disease"],"prefix":"10.1002","volume":"79","author":[{"given":"Vincenzo","family":"Donadio","sequence":"first","affiliation":[{"name":"IRCCS Istituto delle Scienze Neurologiche Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Incensi","sequence":"additional","affiliation":[{"name":"IRCCS Istituto delle Scienze Neurologiche Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Piccinini","sequence":"additional","affiliation":[{"name":"IRCCS Istituto delle Scienze Neurologiche Bologna 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