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Erythrocytic alpha-synuclein in early Parkinson's disease: A 3-year longitudinal study

  • Author Footnotes
    1 These authors contributed equally to this work.
    Genliang Liu
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Center for Movement Disorders, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No.119 Nansihuan, Beijing, 100070, China

    China National Clinical Research Center for Neurological Diseases, Beijing, China
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this work.
    Zhenwei Yu
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
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  • Liyan Gao
    Affiliations
    Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
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  • Yuanchu Zheng
    Affiliations
    Center for Movement Disorders, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No.119 Nansihuan, Beijing, 100070, China

    China National Clinical Research Center for Neurological Diseases, Beijing, China
    Search for articles by this author
  • Tao Feng
    Correspondence
    Corresponding author. Center for Movement Disorders, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China.
    Affiliations
    Center for Movement Disorders, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No.119 Nansihuan, Beijing, 100070, China

    China National Clinical Research Center for Neurological Diseases, Beijing, China
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this work.

      Highlights

      • We showed that total and oligomeric α-synuclein in erythrocyte were elevated even in the initial motor stage of PD.
      • We also showed that higher erythrocytic oligomeric α-synuclein levels at baseline predicts a faster clinical decline over time in patients with early PD.

      Abstract

      Background

      Early diagnosis of Parkinson's disease (PD) could significantly improve outcomes for patients and future disease-modifying treatments. Several studies have revealed that α-synuclein levels in peripheral erythrocytes are associated with PD, but the diagnostic value in early PD is still unknown.

      Methods

      This study included both cross-sectional and longitudinal design. The subjects included 45 patients with early PD and 79 age-matched healthy controls. Participants were re-examined with repeated blood collection and clinical assessments after 3 years. The electrochemiluminescence assay was used to measure total and oligomeric α-synuclein levels respectively. The diagnostic value of erythrocytic α-synuclein for early PD was determined by receiver operator characteristic (ROC) curve. Correlations between RBC α-synuclein levels and changes over 3 years in clinical characteristic scores were further investigated with a linear regression.

      Results

      Total and oligomeric α-synuclein levels in erythrocyte were significantly increased in early PD groups compared with control group (Total α-synuclein, p < 0.001; Oligomer, p < 0.001). Levels of total and oligomeric α-synuclein in erythrocytes were correlated with MDS-UPDRS III scores in early PD (Total α-synuclein, p = 0.008; Oligomer, p = 0.037). After adjusting for age, gender and dopaminergic medication, an association was found between higher erythrocytic oligomeric α-synuclein levels at baseline and greater increase in MDS-UPDRS III scores over 3 years (p = 0.007).

      Conclusion

      Our study suggests that total and oligomeric α-synuclein in erythrocyte were elevated even in the initial motor stage of PD. Higher erythrocytic oligomeric α-synuclein levels at baseline predicts a faster clinical decline over time in patients with early PD.

      Keywords

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      References

        • Bloem B.R.
        • Okun M.S.
        • Klein C.
        Parkinson's disease.
        Lancet. 2021; 397: 2284-2303
        • Rizzo G.
        • Copetti M.
        • Arcuti S.
        • Martino D.
        • Fontana A.
        • Logroscino G.
        Accuracy of clinical diagnosis of Parkinson disease: a systematic review and meta-analysis.
        Neurology. 2016; 86: 566-576
        • Knudsen K.
        • Fedorova T.D.
        • Hansen A.K.
        • Sommerauer M.
        • Otto M.
        • Svendsen K.B.
        • et al.
        In-vivo staging of pathology in REM sleep behaviour disorder: a multimodality imaging case-control study.
        Lancet Neurol. 2018; 17: 618-628
        • Braak H.
        • Del Tredici K.
        Neuropathological staging of brain pathology in sporadic Parkinson's disease: separating the wheat from the chaff.
        J. Parkinsons Dis. 2017; 7: S71-S85
        • Polymeropoulos M.H.
        • Lavedan C.
        • Leroy E.
        • Ide S.E.
        • Dehejia A.
        • Dutra A.
        • et al.
        Mutation in the alpha-synuclein gene identified in families with Parkinson's disease.
        Science. 1997; 276: 2045-2047
        • Chahine L.M.
        • Beach T.G.
        • Brumm M.C.
        • Adler C.H.
        • Coffey C.S.
        • Mosovsky S.
        • et al.
        In vivo distribution of alpha-synuclein in multiple tissues and biofluids in Parkinson disease.
        Neurology. 2020; 95: e1267-e1284
        • Mollenhauer B.
        • Caspell-Garcia C.J.
        • Coffey C.S.
        • Taylor P.
        • Singleton A.
        • Shaw L.M.
        • et al.
        Longitudinal analyses of cerebrospinal fluid alpha-Synuclein in prodromal and early Parkinson's disease.
        Mov. Disord. 2019; 34: 1354-1364
        • Yu Z.
        • Liu G.
        • Li Y.
        • Arkin E.
        • Zheng Y.
        • Feng T.
        Erythrocytic alpha-synuclein species for Parkinson's disease diagnosis and the correlations with clinical characteristics.
        Front. Aging Neurosci. 2022; 14827493
        • Adler C.H.
        • Serrano G.E.
        • Zhang N.
        • Hinni M.L.
        • Lott D.G.
        • Mehta S.H.
        • et al.
        Feasibility of repeat and bilateral submandibular gland needle biopsies in Parkinson's disease.
        Park. Relat. Disord. 2019; 68: 69-72
        • Chung S.J.
        • Konig I.R.
        • Lohmann K.
        • Hinrichs F.
        • Kim J.
        • Ryu H.S.
        • et al.
        Association of SNCA variants with alpha-synuclein of gastric and colonic mucosa in Parkinson's disease.
        Park. Relat. Disord. 2019; 61: 151-155
        • Wang X.
        • Yu S.
        • Li F.
        • Feng T.
        Detection of alpha-synuclein oligomers in red blood cells as a potential biomarker of Parkinson's disease.
        Neurosci. Lett. 2015; 599: 115-119
        • Li X.Y.
        • Yang W.W.
        • Li X.
        • Li X.R.
        • Chen Z.G.
        • Wang C.D.
        • et al.
        Levels of oligomeric alpha-synuclein in red blood cells are elevated in patients with Parkinson's disease and affected by brain alpha-synuclein expression.
        Int. J. Clin. Exp. Med. 2019; 12: 10470-10477
        • Tian C.
        • Liu G.
        • Gao L.
        • Soltys D.
        • Pan C.
        • Stewart T.
        • et al.
        Erythrocytic alpha-Synuclein as a potential biomarker for Parkinson's disease.
        Transl. Neurodegener. 2019; 8: 15
        • Mollenhauer B.
        • Batrla R.
        • El-Agnaf O.
        • Galasko D.R.
        • Lashuel H.A.
        • Merchant K.M.
        • et al.
        A user's guide for alpha-synuclein biomarker studies in biological fluids: Perianalytical considerations.
        Mov. Disord. 2017; 32: 1117-1130
        • Parnetti L.
        • Gaetani L.
        • Eusebi P.
        • Paciotti S.
        • Hansson O.
        • El-Agnaf O.
        • et al.
        CSF and blood biomarkers for Parkinson's disease.
        Lancet Neurol. 2019; 18: 573-586
        • Barbour R.
        • Kling K.
        • Anderson J.P.
        • Banducci K.
        • Cole T.
        • Diep L.
        • et al.
        Red blood cells are the major source of alpha-synuclein in blood.
        Neurodegener. Dis. 2008; 5: 55-59
        • Pretorius E.
        • Swanepoel A.C.
        • Buys A.V.
        • Vermeulen N.
        • Duim W.
        • Kell D.B.
        Eryptosis as a marker of Parkinson's disease.
        Aging (Albany NY). 2014; 6: 788-819
        • Savica R.
        • Grossardt B.R.
        • Carlin J.M.
        • Icen M.
        • Bower J.H.
        • Ahlskog J.E.
        • et al.
        Anemia or low hemoglobin levels preceding Parkinson disease: a case-control study.
        Neurology. 2009; 73: 1381-1387
        • Scherzer C.R.
        • Grass J.A.
        • Liao Z.
        • Pepivani I.
        • Zheng B.
        • Eklund A.C.
        • et al.
        GATA transcription factors directly regulate the Parkinson's disease-linked gene alpha-synuclein.
        Proc. Natl. Acad. Sci. U. S. A. 2008; 105: 10907-10912
        • Niu M.
        • Li Y.
        • Li G.
        • Zhou L.
        • Luo N.
        • Yao M.
        • et al.
        A longitudinal study on alpha-synuclein in plasma neuronal exosomes as a biomarker for Parkinson's disease development and progression.
        Eur. J. Neurol. 2020; 27: 967-974
        • Lee P.H.
        • Lee G.
        • Park H.J.
        • Bang O.Y.
        • Joo I.S.
        • Huh K.
        The plasma alpha-synuclein levels in patients with Parkinson's disease and multiple system atrophy.
        J. Neural. Transm. (Vienna). 2006; 113: 1435-1439
        • Simuni T.
        • Siderowf A.
        • Lasch S.
        • Coffey C.S.
        • Caspell-Garcia C.
        • Jennings D.
        • et al.
        Longitudinal change of clinical and biological measures in early Parkinson's disease: Parkinson's progression markers initiative cohort.
        Mov. Disord. 2018; 33: 771-782