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The objective of this study was to determine the elevation of plasma p62 protein levels in patients with Charcot\u2013Marie\u2013Tooth disease 1A (CMT1A) for its clinical usefulness to assess disease severity. We collected blood samples from 69 CMT1A patients and 59 healthy controls. Plasma concentrations of p62 were analyzed by ELISA, and we compared them with Charcot-Marie-Tooth neuropathy score version 2 (CMTNSv2). A mouse CMT1A model (C22) was employed to determine the source and mechanism of plasma p62 elevation. Plasma p62 was detected in healthy controls with median value of 1978 pg\/ml, and the levels were significantly higher in CMT1A (2465\u00a0pg\/ml, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). The elevated plasma p62 levels were correlated with CMTNSv2 (<jats:italic>r<\/jats:italic>\u2009=\u20090.621, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), motor nerve conduction velocity (<jats:italic>r<\/jats:italic>\u2009=\u2009\u2009\u2212\u20090.490, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) and disease duration (<jats:italic>r<\/jats:italic>\u2009=\u20090.364, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01). In C22 model, increased p62 expression was observed not only in pathologic Schwann cells but also in plasma. Our findings indicate that plasma p62 measurement could be a valuable tool for evaluating CMT1A severity and Schwann cell pathology.<\/jats:p>","DOI":"10.1038\/s41598-024-61794-w","type":"journal-article","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T06:01:59Z","timestamp":1715666519000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["p62\/sequestosome-1 as a severity-reflecting plasma biomarker in Charcot\u2013Marie\u2013Tooth disease type 1A"],"prefix":"10.1038","volume":"14","author":[{"given":"Byeol-A","family":"Yoon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Hee","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo Hyun","family":"Nam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye-Jin","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong-il","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Namhee","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyeong-Hee","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Rae","family":"Jo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong Kuk","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung-Ok","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hwan Tae","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,14]]},"reference":[{"key":"61794_CR1","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1136\/jnnp-2014-308826","volume":"86","author":"V Fridman","year":"2015","unstructured":"Fridman, V. et al. CMT subtypes and disease burden in patients enrolled in the inherited neuropathies consortium natural history study: A cross-sectional analysis. J. Neurol. Neurosurg. Psychiatry 86, 873\u2013878 (2015).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"61794_CR2","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1111\/j.1529-8027.2011.00350.x","volume":"16","author":"SM Murphy","year":"2011","unstructured":"Murphy, S. M. et al. Reliability of the CMT neuropathy score (second version) in Charcot\u2013Marie\u2013Tooth disease. J. Peripheral Nervous Syst. 16, 191\u2013198 (2011).","journal-title":"J. Peripheral Nervous Syst."},{"key":"61794_CR3","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1111\/ene.14689","volume":"28","author":"E Millere","year":"2021","unstructured":"Millere, E. et al. Plasma neurofilament light chain as a potential biomarker in Charcot\u2013Marie\u2013Tooth disease. Eur. J. Neurol. 28, 974\u2013981 (2021).","journal-title":"Eur. J. 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