Neurochemical Research

, Volume 24, Issue 12, pp 1531–1534 | Cite as

Prothrombin Concentration in the Cerebrospinal Fluid Is Not Altered in Alzheimer's Disease

  • P. Lewczuk
  • J. Wiltfang
  • M. Lange
  • H. Jahn
  • H. Reiber
  • H. EhrenreichEmail author


Prothrombin, known to be expressed in brain and to possess growth modulating properties, has been suggested to be involved in the pathogenesis of Alzheimer's disease (AD). We studied prothrombin concentration in lumbar CSF (L-CSF) in patients with AD (n = 25), neurologic disease controls (NDC; n = 33) covering a wide range of neurologic disorders, and subjects with Guillain-Barré syndrome (GBS; n = 4) as well as in samples of non-pathological ventricular CSF (V-CSF; n = 4). The results were evaluated with respect to CSF flow rate, as indicated by the albumin quotient (QAlb). The concentrations of prothrombin in L-CSF in NDC (mean: 0.46 mg/l, range: 0.21–0.96), and AD (mean: 0.6 mg/l, range: 0.19–1.2) were in the normal range reported previously. Expectedly, prothrombin concentration in L-CSF of GBS was increased (mean: 6.3 mg/l, range: 2.3–9.7) corresponding to the increased QAlb in this group (mean 54.6 × 10−3, range: 17–88.1). The concentrations of both prothrombin and albumin were 5.5-fold higher in L-CSF than in V-CSF (mean QAlb : 1.1 × 10−3, mean concentration of prothrombin: 0.088 mg/l). In conclusion, CSF prothrombin in all conditions evaluated here is exclusively derived from blood.

Prothrombin ELISA cerebrospinal fluid blood-CSF barrier Alzheimer neurological disorders 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Goldsack, N. R., Chambers, R. C., Dabbagh, K., and Laurent, G. J. 1998. Thrombin. Int. J. Biochem. Cell Biol. 30:641–646.Google Scholar
  2. 2.
    Fenton, J. W., 2nd, Ofosu, F. A., Brezniak, D. V., and Hassouna, H. I. 1998. Thrombin and antithrombotics. Semin. Thromb. Hemost. 24:87–91.Google Scholar
  3. 3.
    Turgeon, V. L., and Houenou, L. J. 1997. The role of thrombin-like (serine) proteases in the development, plasticity and pathology of the nervous system. Brain Res. Brain Res. Rev. 25:85–95.Google Scholar
  4. 4.
    Sekiya, F., Usui, H., Inoue, K., Fukudome, K., and Morita, T. 1994. Activation of prothrombin by a novel membrane-associated protease. An alternative pathway for thrombin generation independent of the coagulation cascade. J. Biol. Chem. 269:32441–32445.Google Scholar
  5. 5.
    Akiyama, H., Ikeda, K., Kondo, H., and McGeer, P. L. 1992. Thrombin accumulation in brains of patients with Alzheimer's disease. Neurosci. Lett. 146:152–154.Google Scholar
  6. 6.
    Wang, X., An, S., and Wu, J. M. 1996. Specific processing of native and phosphorylated tau protein by proteases. Biochem. Biophys. Res. Commun. 219:591–597.Google Scholar
  7. 7.
    Haas, C., Aldudo, J., Cazorla, P., Bullido, M. J., de Miguel, C., Vazquez, J., and Valdivieso, F. 1997. Proteolysis of Alzheimer's disease beta-amyloid precursor protein by factor Xa. Biochim. Biophys. Acta. 1343:85–94.Google Scholar
  8. 8.
    Smirnova, I. V., Salazar, A., Arnold, P. M., Glatt, S., Handler, M., and Festoff, B. W. 1997. Thrombin and its precursor in human cerebrospinal fluid. Thromb. Haemost. 78:1473–1479.Google Scholar
  9. 9.
    Lewczuk, P., Reiber, H., and Ehrenreich, H. 1998. Prothrombin in normal human cerebrospinal fluid originates from the blood. Neurochem. Res. 23:1027–1030.Google Scholar
  10. 10.
    Nemetz, P. N., Leibson, C., Naessens, J. M., Beard, M., Kokmen, E., Annegers, J. F., and Kurland, L. T. 1999. Traumatic brain injury and time to onset of Alzheimer's disease: a population-based study. Am. J. Epidemiol. 149:32–40.Google Scholar
  11. 11.
    Wagner, S. L., Geddes, J. W., Cotman, C. W., Lau, A. L., Gurwitz, D., Isackson, P. J., and Cunningham, D. D. 1989. Protease nexin-1, an antithrombin with neurite outgrowth activity, is reduced in Alzheimer disease. Proc. Natl. Acad. Sci. USA 86:8284–8288.Google Scholar
  12. 12.
    Reiber, H. 1995. Die diagnostische Bedeutung neuroimmunologischer Reaktionsmuster im Liquor cerebrospinalis. Lab. Med. 19:444–462.Google Scholar
  13. 13.
    American Psychiatric Association (APA) 1994. Diagnostic and statistical manual of mental disorders. Washington DC.Google Scholar
  14. 14.
    McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., and Stadlan, E. M. 1984. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 34:939–944.Google Scholar
  15. 15.
    Folstein, M. F., Folstein, S. E., and McHugh, P. R. 1975. “Minimental state”. A practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res. 12:189–198.Google Scholar
  16. 16.
    Reiber, H. 1994. Flow rate of cerebrospinal fluid (CSF)—a concept common to normal blood-CSF barrier function and to dysfunction in neurological diseases. J. Neurol. Sci. 122:189–203.Google Scholar

Copyright information

© Plenum Publishing Corporation 1999

Authors and Affiliations

  • P. Lewczuk
    • 1
    • 2
  • J. Wiltfang
    • 1
  • M. Lange
    • 3
  • H. Jahn
    • 4
  • H. Reiber
    • 2
  • H. Ehrenreich
    • 1
    Email author
  1. 1.Max-Planck-Institute for Experimental Medicine and Departments of Psychiatry and NeurologyGeorg-August-UniversityGöttingen
  2. 2.Neurochemistry LaboratoryGeorg-August-UniversityGöttingen
  3. 3.Department of NeurosurgeryKlinikum Villingen-SchwenningenGermany
  4. 4.Department of PsychiatryUniversity of HamburgGermany

Personalised recommendations