Journal of Neural Transmission

, Volume 124, Issue 3, pp 353–360 | Cite as

Relationship between the plasma levels of neurodegenerative proteins and motor subtypes of Parkinson’s disease

  • Jian Ding
  • Jiejin Zhang
  • Xixi Wang
  • Li Zhang
  • Siming Jiang
  • Yongsheng Yuan
  • Junyi Li
  • Lin Zhu
  • Kezhong ZhangEmail author
Neurology and Preclinical Neurological Studies - Original Article


The aim of our study is to examine the plasma levels of the four kinds of neurodegenerative proteins in plasma: α-syn, T-tau, P-tau181, and Aβ-42 in Parkinson’s disease (PD) and to evaluate the relationship between their plasma levels and PD motor subtypes. 84 patients with PD were enrolled in our study, and finally, 73 of them were classified into the tremor-dominant subtype (TD) and the postural instability gait difficulty subtype (PIGD). Their motor performance was evaluated by a series of clinical assessments: Freezing of Gait Questionnaire (FOGQ), Timed Up and Go (TUGs), Tinetti balance, and Tinetti gait. Plasma levels of these proteins were measured by enzyme-linked immunosorbent assay (ELISA). The plasma level of α-syn was significantly higher in PD patients when compared to controls (p = 0.004), and significantly higher in the PIGD group when compared to the TD group (p = 0.03). While the plasma level of Aβ-42 was significantly lower in PD patients than in controls (p = 0.002), and significantly lower in the PIGD group than in the TD group (p = 0.05). In PD patients, the plasma level of α-syn (r = −0.355, p < 0.001) was significantly related to the severity of Tenitti Gait score, even after performing multiple linear regression (p = 0.002). While the plasma level of Aβ-42 (r = −0.261, p < 0.05) was significantly associated with the severity of PIGD score and remained correlate when performed multiple linear regression (p = 0.005). The patients with PIGD subtype are characterized with a lower level of plasma Aβ-42 and a higher plasma level of α-syn, which may be used as biomarkers for diagnosis and progression of the subtypes of PD.


Parkinson’s disease Postural instability gait difficulty subtype Tremor-dominant subtype Neurodegenerative proteins 



This work was supported by the Natural science foundation of Jiangsu Province (No. BK20141494), the Jiangsu Provincial Personnel Department “the Great of Six Talented Man Peak” Project (No. 2014-WSN-013), the University Natural Science Research Project in Jiangsu Province (No. 13KJB32009), the Opening Project of Jiangsu Key Laboratory of Neurodegeneration (No. SJ11KF01),and Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) and Science and Technology Project of Jiangsu Bureau of Traditional Chinese Medicine (No. YB2015163).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Alves G, Pedersen KF, Bloem BR et al (2013) Cerebrospinal fluid amyloid-beta and phenotypic heterogeneity in de novo Parkinson’s disease. J Neurol Neurosurg Psychiatry 84(5):537–543CrossRefPubMedGoogle Scholar
  2. Atik A, Stewart T, Zhang J (2016) Alpha-Synuclein as a Biomarker for Parkinson’s Disease. Brain Pathol 26(3):410–418CrossRefPubMedGoogle Scholar
  3. Auyeung M, Tsoi TH, Mok V et al (2012) Ten year survival and outcomes in a prospective cohort of new onset Chinese Parkinson’s disease patients. J Neurol Neurosurg Psychiatry 83(6):607–611CrossRefPubMedGoogle Scholar
  4. Besong-Agbo D, Elias W, Frank J et al (2013) Naturally occurring a-synuclein autoantibody levels are lower in patients with Parkinson disease. Neurology 80:169–175CrossRefPubMedGoogle Scholar
  5. Bohnen NI, Cham R (2006) Postural control, gait, and dopamine functions in parkinsonian movement disorders. Clin Geriatr Med 22(4):797–812 (vi) CrossRefPubMedGoogle Scholar
  6. Campbell MC, Koller JM, Snyder AZ et al (2015) CSF proteins and resting-state functional connectivity in Parkinson disease. Neurology 84:2413–2421CrossRefPubMedPubMedCentralGoogle Scholar
  7. Duran R, Francisco JB, Blas M et al (2010) Plasma a-synuclein in patients with Parkinson’s disease with and without treatment. Mov Disord 25:489–493CrossRefPubMedGoogle Scholar
  8. Fahn S, Elton RL, Committee UD (1987) Unified Parkinson’s disease rating scale. Recent Dev Parkinson's Dis 2:153–163Google Scholar
  9. Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12(3):189–198CrossRefPubMedGoogle Scholar
  10. Foulds PG, Mitchell D, Parker A et al (2011) Phosphorylated -synuclein can be detected in blood plasma and is potentially a useful biomarker for Parkinson’s disease. FASEB J 25:4127–4137CrossRefPubMedGoogle Scholar
  11. Gruden MA, Davidova TV, Yanamandra K et al (2013) Nasal inoculation with alpha-synuclein aggregates evokes rigidity, locomotor deficits and immunity to such misfolded species as well as dopamine. Behav Brain Res 243:205–212CrossRefPubMedGoogle Scholar
  12. Hanakawa T, Katsumi Y, Fukuyama H et al (1999) Mechanisms underlying gait disturbance in Parkinson’s disease: a single photon emission computed tomography study. Brain 122(Pt 7):1271–1282CrossRefPubMedGoogle Scholar
  13. Hoehn MM, Yahr MD (1967) Parkinsonism: onset, progression and mortality. Neurology 17(5):427–442CrossRefPubMedGoogle Scholar
  14. Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55(3):181–184CrossRefPubMedPubMedCentralGoogle Scholar
  15. Iacono RP, Kuniyoshi SM, Ahlman JR, Zimmerman GJ, Maeda G, Pearlstein RD et al (1997) Concentrations of indoleamine metabolic intermediates in the ventricular cerebrospinal fluid of advanced Parkinson’s patients with severe postural instability and gait disorders. J Neural Transm (Vienna) 104(4–5):451–459CrossRefGoogle Scholar
  16. Jankovic J, McDermott M, Carter J et al (1990) Variable expression of Parkinson’s disease: a base-line analysis of the DATATOP cohort. The Parkinson Study Group. Neurology 40(10):1529–1534CrossRefPubMedGoogle Scholar
  17. Jellinger KA (2012) CSF biomarkers in different phenotypes of Parkinson disease. J Neural Transm (Vienna) 119(4):455–456CrossRefGoogle Scholar
  18. Kang JH, Irwin DJ, Chen-Plotkin AS et al (2013) Association of cerebrospinal fluid beta-amyloid 1–42, T-tau, P-tau181, and alpha-synuclein levels with clinical features of drug-naive patients with early Parkinson disease. JAMA Neurol 70(10):1277–1287PubMedPubMedCentralGoogle Scholar
  19. Karin DD, Wesley J, Johennes AH et al (2013) Cerebrospinal fliud and plasma clusterin levels in Parkinson’s disease. Parkinsonism Relat Disord 19(12):1079–1083CrossRefGoogle Scholar
  20. Kegelmeyer DA, Kloos AD, Thomas KM et al (2007) Reliability and validity of the Tinetti Mobility Test for individuals with Parkinson disease. Phys Ther 87(10):1369–1378CrossRefPubMedGoogle Scholar
  21. Lee PH, Lee G, Park HJ et al (2006) The plasma alpha-synuclein levels in patients with Parkinson’s disease and multiple system atrophy. J Neural Transm (Vienna) 113(10):1435–1439CrossRefGoogle Scholar
  22. Lehallier B, Essioux L, Gayan J et al (2015) Combined plasma and cerebrospinal fluid signature for the prediction of midterm progression from mild cognitive impairment to Alzheimer disease. JAMA Neurol 2015:1–10Google Scholar
  23. Li QX, Mok SS, Laughton KM et al (2007) Plasma α-synuclein is decreased in subjects with Parkinson’s disease. Exp Neurol 204:583–588CrossRefPubMedGoogle Scholar
  24. Majbour NK, Vaikath NN, Eusebi P et al (2016) Longitudinal changes in CSF alpha-synuclein species reflect Parkinson’s disease progression. Mov Disord 31(10):1535–1542CrossRefPubMedGoogle Scholar
  25. Menzie J, Pan C, Prentice H et al (2014) Taurine and central nervous system disorders. Amino Acids 46(1):31–46CrossRefPubMedGoogle Scholar
  26. Molina JA, Jiménez-Jiménez FJ, Gomez P et al (1997) Decreased cerebrospinal fluid levels of neutral and basic amino acids in patients with Parkinson's disease. J Neurol Sci 150(2):123–127CrossRefPubMedGoogle Scholar
  27. Ohrfelt A, Grognet P, Andreasen N et al (2009) Cerebrospinal fluid alpha-synuclein in neurodegenerative disorders-a marker of synapse loss? Neurosci Lett 450(3):332–335CrossRefPubMedGoogle Scholar
  28. Park MJ, Cheon SM, Bae HR et al (2011) Elevated levels of α-synuclein oligomer in the cerebrospinal fluid of drug-naïve patients with Parkinson’s disease. J Clin Neurol 7:215–222CrossRefPubMedPubMedCentralGoogle Scholar
  29. Parkkinen L, Soininen H, Laakso M et al (2001) Alpha-synuclein pathology is highly dependent on the case selection. Neuropathol Appl Neurobiol 27(4):314–325CrossRefPubMedGoogle Scholar
  30. Ritz B, Rhodes SL, Bordelon Y et al (2012) a-synuclein genetic variants predict faster motor. Symptom progression in idiopathic Parkinson disease. PLoS One 7:e36199CrossRefPubMedPubMedCentralGoogle Scholar
  31. Shumway-Cook A, Brauer S, Woollacott M (2000) Predicting the probability for falls in community-dwelling older adults using the Timed Up & Go Test. Phys Ther 80(9):896–903PubMedGoogle Scholar
  32. Spillantini MG (1997) a-Synuclein in Lewy bodies. Nature 399:839–840CrossRefGoogle Scholar
  33. Tomlinson CL, Stowe R, Patel S et al (2010) Systematic review of levodopa dose equivalency reporting in Parkinson’s disease. Mov Disord 25(15):2649–2653CrossRefPubMedGoogle Scholar
  34. Wang XY, Kang WY, Yang Q et al (2014) Using gastrocnemius sEMG and plasma alpha-synuclein for the prediction of freezing of gait in Parkinson’s disease patients. PLoS One 9(2):e89353CrossRefPubMedPubMedCentralGoogle Scholar
  35. Yu X, He GR, Sun L et al (2012) Assessment of the treatment effect of baicalein on a model of Parkinsonian tremor and elucidation of the mechanism. Life Sci 91(1–2):5–13CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  • Jian Ding
    • 1
  • Jiejin Zhang
    • 1
  • Xixi Wang
    • 1
  • Li Zhang
    • 1
  • Siming Jiang
    • 1
  • Yongsheng Yuan
    • 1
  • Junyi Li
    • 1
  • Lin Zhu
    • 1
  • Kezhong Zhang
    • 1
    Email author
  1. 1.Department of NeurologyThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina

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