Laboratory Markers of Neurodegneration in Cerebrospinal Fluid and Degree of Motor Involvement in Parkinson Disease: A Correlation Study

Česká verzia

Authors: H. Vranová ¹; P. Kaňovský ¹; J. Mareš ¹; M. Nevrlý ¹; D. Stejskal ^2,3; I. Nestrašil ¹; J. Zapletalová ⁴
Authors place of work: Neurologická klinika LF UP a FN Olomouc ¹; Oddělení laboratorní medicíny, Nemocnice Šternberk o. z., Středomoravská nemocniční a. s. ²; Ústav lékařské chemie a biochemie LF UP Olomouc ³; Ústav lékařské biofyziky LF UP Olomouc ⁴
Published in the journal: Cesk Slov Neurol N 2008; 71/104(3): 324-328
Category: Short Communication

Summary

Parkinson disease (PD) is a progressive degenerative illness of the nervous system. Patients with this illness undergo a progress of neurological degeneration leading to morphological and neurochemical changes in the central nervous system. The Braak concept divides this pathology into six stages which are correlated with clinical assessment using the Hoehn-Yahr scale. The severity of neurodegeneration is known to correlate with certain laboratory indicators in CSF. The aim of this study was to assess tau-protein, beta-amyloid_(1–42) and cystatin C CSF levels in patients suffering from PD and in the control group and to compare CSF levels between these two groups and correlate to both the duration and severity of motor impairment in PD. Tau-protein, beta-amyloid_(1–42) and cystatin C in CSF were assessed and the tau-protein/beta-amyloid_(1–42) ratio was calculated in 32 patients suffering from PD and in a control group (CG) of 20 patients. The following statistically significant differences in the CSF were found: higher tau-protein levels in PD patients versus CG (p = 0.05), higher tau-protein levels (p = 0.03) and tau-protein/beta-amyloid_(1–42) ratio (p = 0.01) in PD patients with duration less than 2 years vs. PD with duration more than 2 years. No significant correlation was found between the tau-protein CSF levels and the severity of motor manifestation of PD. No difference in levels of beta-amyloid_(1–42) and cystatin C in CSF was found in the CG and PD patients groups. Presented study indicates an important role for the tau-protein CSF level evaluation as a marker of neurodegeneration in PD patients, especially within the first two years of the appearance of clinical symptoms.

Key words:
Parkinson disease – tau-protein – beta-amyloid – cystatin C – CSF

Zdroje

1. Růžička E, Roth J, Kaňovský P et al. Extrapyramidová onemocnění 1. Parkinsonova nemoc a Parkinsonské syndromy. Praha: Galén 2000.

2. Arima K, Hirai S, Sunohara N, Aoto K, Izumiyama Y, Ueda K et al. Cellular co-localization of phosphorylated tau- and NACP/alpha-synuclein-epitopes in Lewy bodies in sporadic Parkinson's disease and in dementia with Lewy bodies. Brain Res 1999; 843(1–2): 53–61.

3. Ishizawa T, Mattila P, Davies P, Wang D, Dickson DW. Colocalization of tau and alpha-synuclein epitopes in Lewy bodies. J Neuropathol Exp Neurol 2003; 62(4): 389–397.

4. Esposito A, Dohm CP, Kermer P, Bähr M, Wouters FS. Alpha-Synuclein and its disease-related mutants interact differentially with the microtubule protein tau and associate with the actin cytoskeleton. Neurobiol Dis 2007; 26(3): 521–531.

5. Jensen PH, Hager H, Nielsen MS, Hojrup P, Gliemann J, Jakes R. Alpha-synuclein binds to Tau and stimulates the protein kinase A-catalyzed tau phosphorylation of serine residues 262 and 356. J Biol Chem 1999; 274(36): 25481–25489.

6. Braak H, Del Tredici K, Rüb U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain patology related to sporadic Parkinson’s disease. Neurobiology of Aging 2003; 24(2): 197–211.

7. Braak H, Ghebremedhin E, Rub U, Bratzke H, Del Tredici K. Stages in the development of Parkinson's disease-related pathology. Cell Tissue Res 2004; 318(1): 121–134.

8. Muller J, Wenning GK, Jellinger K, McKee A, Poewe W, Litvan I. Progression of Hoehn and Yahr stages in Parkinsonian disorders: a clinicopathologic study. Neurology 2000; 55(6): 888–891.

9. Bibl M, Mollenhauer B, Esselmann H, Lewczuk P, Klafki HW, Sparbier K et al. CSF amyloid-beta-peptides in Alzheimer's disease, dementia with Lewy bodies and Parkinson's disease dementia. Brain 2006; 129(Pt 5): 1177–1187.

10. Portelius E, Zetterberg H, Andreasson U, Brinkmalm G, Andreasen N, Wallin A et al. An Alzheimer's disease-specific beta-amyloid fragment signature in cerebrospinal fluid. Neurosci Lett 2006; 409(3): 215–219.

11. Stejskal D, Vavroušková J, Mareš J, Urbánek K. Application of new laboratory marker assays in neurological diagnosis - a pilot study. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2005; 149(2): 265–266.

12. Mareš J, Stejskal D, Vavrouškova J, Urbánek K, Herzig R, Hluštík P. Use of cystatin C determination in clinical diagnostics. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2003; 147(2): 177–180.

13. Mareš J, Herzig R, Urbánek K, Vranová H, Hluštík P, Stejskal D et al. Využití stanovení cystatinu C u pacientů s neurodegenerativním chorobami. Cesk Slov Neurol N 2006; 69/102(3): 195–199.

14. Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 1992; 55(3): 181–184.

15. Molina JA, Benito-Leon J, Jimenez-Jimenez FJ, Ortí-Pareja M, Berbel A, Tallón-Barranco A et al. Tau protein concentrations in cerebrospinal fluid of non-demented Parkinson's disease patients. Neurosci Lett 1997; 238(3): 139–141.

16. Yang W, Ang LC, Strong MJ. Tau protein aggregation in the frontal and entorhinal cortices as a function of aging. Brain Res Dev Brain Res 2005; 156(2): 127–138.

17. Mollenhauer B, Trenkwalder C, von Ahsen N, Bibl M, Steinacker P, Brechlin P et al. Beta-amlyoid 1-42 and tau-protein in cerebrospinal fluid of patients with Parkinson's disease dementia. Dement Geriatr Cogn Disord 2006; 22(3): 200–208.

18. Fagan AM, Roe CM, Xiong C, Mintun MA, Morris JC, Holtzman DM et al. Cerebrospinal fluid tau/beta-amyloid(42) ratio as a prediction of cognitive decline in nondemented older adults. Arch Neurol 2007; 64(3): 343–349.