{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:11:17Z","timestamp":1790705477372,"version":"4.1.0"},"reference-count":90,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T00:00:00Z","timestamp":1714521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Cutaneous phosphorylated alpha-synuclein (p-\u03b1-syn) deposition is an important biomarker of idiopathic Parkinson\u2019s disease (iPD). Recent studies have reported synucleinopathies in patients with common genetic forms of PD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aimed to detect p-\u03b1-syn deposition characteristic in rare genetic PD patients with <jats:italic>CHCHD2<\/jats:italic> or <jats:italic>RAB39B<\/jats:italic> mutations. Moreover, this study also aimed to describe peripheral alpha-synuclein prion-like activity in genetic PD patients, and acquire whether the cutaneous synucleinopathy characteristics of genetic PD are consistent with central neuropathologies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed four skin biopsy samples from the distal leg (DL) and proximal neck (C7) of 161 participants, including four patients with <jats:italic>CHCHD2<\/jats:italic> mutations, two patients with <jats:italic>RAB39B<\/jats:italic> mutations, 16 patients with <jats:italic>PRKN<\/jats:italic> mutations, 14 patients with <jats:italic>LRRK2<\/jats:italic> mutations, five patients with <jats:italic>GBA<\/jats:italic> mutations, 100 iPD patients, and 20 healthy controls. We detected cutaneous synucleinopathies using immunofluorescence staining and a seeding amplification assay (SAA). A systematic literature review was also conducted, involving 64 skin biopsies and 205 autopsies of genetic PD patients with synucleinopathy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>P-\u03b1-syn was deposited in the peripheral cutaneous nerves of PD patients with <jats:italic>CHCHD2<\/jats:italic>, <jats:italic>LRRK2<\/jats:italic>, or <jats:italic>GBA<\/jats:italic> mutations but not in those with <jats:italic>RAB39B<\/jats:italic> or <jats:italic>PRKN<\/jats:italic> mutations. There were no significant differences in the location or rate of \u03b1-syn-positive deposits between genetic PD and iPD patients. Peripheral cutaneous synucleinopathy appears to well represent brain synucleinopathy of genetic PD, especially autosomal dominant PD (AD-PD). Cutaneous \u03b1-synuclein SAA analysis of iPD and <jats:italic>LRRK2<\/jats:italic> and <jats:italic>GBA<\/jats:italic> mutation patients revealed prion-like activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>P-\u03b1-syn deposition in peripheral cutaneous nerves, detected using SAA and immunofluorescence staining, may serve as an accurate biomarker for genetic PD and iPD in the future.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2024.1404492","type":"journal-article","created":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T06:10:25Z","timestamp":1714543825000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Peripheral cutaneous synucleinopathy characteristics in genetic Parkinson\u2019s disease"],"prefix":"10.3389","volume":"15","author":[{"given":"Yanpeng","family":"Yuan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minglei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyang","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanjun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengyuan","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuming","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,5,1]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1016\/S0140-6736(14)61393-3","article-title":"Parkinson's 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