AUTHOR=Li Xu-Ying , Li Wei , Li Xin , Li Xu-Ran , Sun Linjuan , Yang Weiwei , Cai Yanning , Chen Zhigang , Wu Jun , Wang Chaodong , Yu Shun 

TITLE=Alterations of Erythrocytic Phosphorylated Alpha-Synuclein in Different Subtypes and Stages of Parkinson's Disease

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=13

YEAR=2021

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2021.623977

DOI=10.3389/fnagi.2021.623977

ISSN=1663-4365

ABSTRACT=<p>Serine 129-phosphorylated alpha-synuclein (pS-α-syn) is a major form of α-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-α-syn (pS-α-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-α-syn-RBC, we demonstrated significantly higher levels of pS-α-syn-RBC in PD patients than in healthy controls. pS-α-syn-RBC separated the patients well from the controls, with a sensitivity of 93.39% (95% CI: 90.17–95.81%), a specificity of 93.11% (95% CI: 89.85–95.58%), and an area under the curve (AUC) of 0.96. Considering motor subtypes, the levels of pS-α-syn-RBC were significantly higher in late-onset than young-onset PD (<italic>p</italic> = 0.013) and in those with postural instability and gait difficulty than with tremor-dominant (TD) phenotype (<italic>p</italic> = 0.029). In addition, the levels of pS-α-syn-RBC were also different in non-motor subtypes, which were significantly lower in patients with cognitive impairment (<italic>p</italic> = 0.012) and olfactory loss (<italic>p</italic> = 0.004) than in those without such symptoms. Moreover, the levels of pS-α-syn-RBC in PD patients were positively correlated with disease duration and Hoehn &amp; Yahr stages (H&amp;Y) (<italic>p</italic> for trend =0.02 and &lt;0.001) as well as UPDRS III (<italic>R</italic><sup>2</sup> = 0.031, <italic>p</italic> = 0.0042) and MoCA scores (<italic>R</italic><sup>2</sup> = 0.048, <italic>p</italic> = 0.0004). The results obtained suggest that pS-α-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.</p>