Journal of Neural Transmission

, Volume 117, Issue 10, pp 1177–1181 | Cite as

CSF markers of neurodegeneration in Parkinson’s disease

  • Hana Přikrylová Vranová
  • Jan Mareš
  • Martin Nevrlý
  • David Stejskal
  • Jana Zapletalová
  • Petr Hluštík
  • Petr Kaňovský
Movement Disorders - Original Article

Abstract

Parkinson’s disease (PD) is a chronic, progressive, neurodegenerative disease with a multifactorial etiology. Protein accumulation is speculated by some to play a prominent role in the pathogenesis of PD. The severity of neurodegeneration should correlate with cerebrospinal fluid (CSF) levels of these neurodegenerative markers (NDMs). The aims of the study were to assess the CSF levels of tau protein, beta-amyloid (1–42), cystatin C, and clusterin in patients suffering from PD and in a control group, to compare the CSF levels between the two groups and to correlate them to PD duration. NDMs in the CSF were assessed in 32 patients suffering from PD and in a control group (CG) of 30 patients. The following statistically significant differences in the CSF were found: higher tau protein (p = 0.045) and clusterin levels (p = 0.004) in PD patients versus CG; higher tau protein levels (p = 0.033), tau protein/beta-amyloid (1–42) ratio (p = 0.011), and clusterin (p = 0.044) in patients suffering from PD for <2 years versus patients suffering PD for more than 2 years. No differences between beta-amyloid (1–42) and cystatin C CSF levels were found in the CG and PD patients groups. Significantly higher tau protein and clusterin CSF levels in the group of PD patients with disease duration of <2 years probably reflect the fact that most neurodegenerative changes in PD patients occur in the initial stage of disease.

Keywords

Parkinson’s disease Tau protein Clusterin CSF Neurodegeneration 

References

  1. Alam ZI, Jenner A, Daniel SE, Lees AJ, Cairns N, Marsden CD et al (1997) Oxidative DNA damage in the parkinsonian brain: an apparent selective increase in 8-hydroxyguanine levels in substantia nigra. J Neurochem 69:1196–1203CrossRefPubMedGoogle Scholar
  2. Arima K, Hirai S, Sunohara N, Aoto K, Izumiyama Y, Ueda K et al (1999) Cellular colocalization of phosphorylated tau- and NACP/alpha-synuclein-epitopes in Lewy bodies in sporadic Parkinson’s disease and in dementia with Lewy bodies. Brain Res 843:53–61CrossRefPubMedGoogle Scholar
  3. Bibl M, Mollenhauer B, Esselmann H, Lewczuk P, Klafki HW, Sparbier K, Smirnov A, Cepek L, Trenkwalder C, Rüther E, Kornhuber J, Otto M, Wiltfang J (2006) CSF amyloid-beta-peptides in Alzheimer’s disease, dementia with Lewy bodies and Parkinson’s disease dementia. Brain 129(Pt 5):1177–1187 cCrossRefPubMedGoogle Scholar
  4. Braak H, Del Tredici K, Rüb U et al (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24:197–211CrossRefPubMedGoogle Scholar
  5. Cookson MR, van der Brug M (2008) Cell systems and the toxic mechanism(s) of alpha-synuclein. Exp Neurol 209:5–11CrossRefPubMedGoogle Scholar
  6. Esposito A, Dohm CP, Kermer P, Bähr M, Wouters FS (2007) alpha-Synuclein and its disease related mutants interact differentially with the microtubule protein tau and associate with the actin cytoskeleton. Neurobiol Dis 26:521–531CrossRefPubMedGoogle Scholar
  7. Fagan AM, Roe CM, Xiong C, Mintun MA, Morris JC, Holtzman DM et al (2007) Cerebrospinal fluid tau/beta-amyloid(42) ratio as a prediction of cognitive decline in nondemented older adults. Arch Neurol 64:343–349CrossRefPubMedGoogle Scholar
  8. 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 55:181–184CrossRefPubMedGoogle Scholar
  9. Jenner P, Olanow CW (2006) The pathogenesis of cell death in Parkinson’s disease. Neurology 66:S24–S36PubMedGoogle Scholar
  10. Mareš J, Stejskal D, Vavrouškova J, Urbánek K, Herzig R, Hluštík P (2003) Use of cystatin C determination in clinical diagnostics. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 147:177–180PubMedGoogle Scholar
  11. Marras C, Lang A (2008) Invited article: changing concepts in Parkinson disease: moving beyond the decade of the brain. Neurology 70(21):1996–2003CrossRefPubMedGoogle Scholar
  12. McNaught KS, Olanow CW (2006) Protein aggregation in the pathogenesis of familial and sporadic Parkinson’s disease. Neurobiol Aging 27:530–545CrossRefPubMedGoogle Scholar
  13. Molina JA, Benito-Leon J, Jimenez-Jimenez FJ et al (1997) Tau protein concentrations in cerebrospinal fluid of non-demented Parkinson’s disease patients. Neurosci Lett 238:139–141CrossRefPubMedGoogle Scholar
  14. Mollenhauer B, Trenkwalder C, von Ahsen N, Bibl M, Steinacker P, Brechlin P et al (2006) Beta-amyloid 1–42 and tau-protein in cerebrospinal fluid of patients with Parkinson’s disease dementia. Dement Geriatr Cogn Disord 22(3):200–208CrossRefPubMedGoogle Scholar
  15. Pucci S, Mazzarelli P, Missiroli F, Regine F, Ricci F (2008) Neuroprotection: VEGF, IL-6, and clusterin: the dark side of the moon. Prog Brain Res 173:555–573CrossRefPubMedGoogle Scholar
  16. Sasaki K, Doh-ura K, Wakisaka Y, Iwaki T (2002) Clusterin/apolipoprotein J is associated with cortical Lewy bodies: immunohistochemical study in cases with alpha-synucleinopathies. Acta Neuropathol 104(3):225–230PubMedGoogle Scholar
  17. Schapira AH (2008) Mitochondria in the aetiology and pathogenesis of Parkinson’s disease. Lancet Neurol 7:97–109CrossRefPubMedGoogle Scholar
  18. Stejskal D, Vavroušková J, Mareš J, Urbánek K (2005) Application of new laboratory marker assays in neurological diagnosis—a pilot study. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 149(2):265–266PubMedGoogle Scholar
  19. Vranová H, Kaňovský P, Mareš J et al (2008) Laboratory markers of neurodegeneration in cerebrospinal fluid and degree of motor involvement in Parkinson’s disease: a correlation study. Cesk Slov Neurol N 71/104(3):324–328Google Scholar
  20. Vranová H, Nevrlý M, Mareš J, Nestrašil I, Stejskal D, Kaňovský P (2009) Neurodegenerative markers in cerebrospinal fluid in Parkinson’s disease. Neurology 72(11 Suppl.3):66Google Scholar
  21. Weintraub D, Comella CL, Horn S (2008) Parkinson’s disease—part 1: pathophysiology, symptoms, burden, diagnosis, and assessment. Am J Manag Care 14(2 Suppl):S40–S48PubMedGoogle Scholar
  22. Yacoubian TA, Standaert DG (2009) Targets for Neuroprotection in Parkinson’s Disease. Biochim Biophys Acta 1792(7):676–687PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Hana Přikrylová Vranová
    • 1
  • Jan Mareš
    • 1
  • Martin Nevrlý
    • 1
  • David Stejskal
    • 2
  • Jana Zapletalová
    • 3
  • Petr Hluštík
    • 1
  • Petr Kaňovský
    • 1
  1. 1.Department of Neurology, Faculty of Medicine and DentistryPalacky University in Olomouc, and University Hospital OlomoucOlomoucCzech Republic
  2. 2.Department of Medical Chemistry and Biochemistry, Faculty of Medicine and DentistryPalacky University in Olomouc, and University Hospital OlomoucOlomoucCzech Republic
  3. 3.Department of Medical Biophysics, Faculty of Medicine and DentistryPalacky University in OlomoucOlomoucCzech Republic

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