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Aging Neurosci."],"abstract":"<jats:p>Serine 129-phosphorylated alpha-synuclein (pS-\u03b1-syn) is a major form of \u03b1-syn relevant to the pathogenesis of Parkinson's disease (PD), which has been recently detected in red blood cells (RBCs). However, alterations of RBC-derived pS-\u03b1-syn (pS-\u03b1-syn-RBC) in different subtypes and stages of PD remains to be investigated. In the present study, by using enzyme-linked immunosorbent assay (ELISA) to measure pS-\u03b1-syn-RBC, we demonstrated significantly higher levels of pS-\u03b1-syn-RBC in PD patients than in healthy controls. pS-\u03b1-syn-RBC separated the patients well from the controls, with a sensitivity of 93.39% (95% CI: 90.17\u201395.81%), a specificity of 93.11% (95% CI: 89.85\u201395.58%), and an area under the curve (AUC) of 0.96. Considering motor subtypes, the levels of pS-\u03b1-syn-RBC were significantly higher in late-onset than young-onset PD (<jats:italic>p<\/jats:italic> = 0.013) and in those with postural instability and gait difficulty than with tremor-dominant (TD) phenotype (<jats:italic>p<\/jats:italic> = 0.029). In addition, the levels of pS-\u03b1-syn-RBC were also different in non-motor subtypes, which were significantly lower in patients with cognitive impairment (<jats:italic>p<\/jats:italic> = 0.012) and olfactory loss (<jats:italic>p<\/jats:italic> = 0.004) than in those without such symptoms. Moreover, the levels of pS-\u03b1-syn-RBC in PD patients were positively correlated with disease duration and Hoehn &amp;amp; Yahr stages (H&amp;amp;Y) (<jats:italic>p<\/jats:italic> for trend =0.02 and &amp;lt;0.001) as well as UPDRS III (<jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup> = 0.031, <jats:italic>p<\/jats:italic> = 0.0042) and MoCA scores (<jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup> = 0.048, <jats:italic>p<\/jats:italic> = 0.0004). The results obtained suggest that pS-\u03b1-syn-RBC can be used as a potential biomarker for not only separating PD patients from healthy controls but also predicting the subtypes and stages of PD.<\/jats:p>","DOI":"10.3389\/fnagi.2021.623977","type":"journal-article","created":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T08:21:01Z","timestamp":1632903661000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":28,"title":["Alterations of Erythrocytic Phosphorylated Alpha-Synuclein in Different Subtypes and Stages of Parkinson's Disease"],"prefix":"10.3389","volume":"13","author":[{"given":"Xu-Ying","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu-Ran","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linjuan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanning","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaodong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"11120","DOI":"10.1038\/srep11120","article-title":"Total and proteinase K-resistant \u03b1-synuclein levels in erythrocytes, determined by their ability to bind phospholipids, associate with Parkinson's disease","volume":"5","author":"Abd-Elhadi","year":"2015","journal-title":"Sci. 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