Protein 14-3-3 Detection in Cerebrospinal Fluid – Clinico-Pathological Correlation

Authors: R. Matěj 1;  J. Nováková 1;  J. Fiala 2;  F. Koukolík 2;  R. Rusina 2
Authors‘ workplace: Národní referenční laboratoř pro diagnostiku lidských prionových chorob při Oddělení patologie a molekulární medicíny, Fakultní Thomayerova nemocnice s poliklinikou, Praha 1;  Neurologická klinika IPVZ a Fakultní Thomayerova nemocnice s poliklinikou, Praha 2
Published in: Cesk Slov Neurol N 2008; 71/104(6): 695-699
Category: Short Communication


The 14-3-3 – protein group is formed by seven isotope signal molecules. The exact function of these molecules is not known yet. Detection of the ß-subunit of the 14-3-3 protein in cerebrospinal fluid is one of the most important paraclinical markers in sporadic Creutzfeldt-Jakob disease (sCJD) diagnostic procedure. This marker is not specific and its specificity and sensitivity are influenced by the timing and technical aspects of sampling and especially by proper indication.

Protein 14-3-3 detection was performed by a standardized method using western blot with chemoluminiscent detection of ß-subunit in cerebrospinal fluid samples from patients with clinical suspection of CJD.

57 cerebrospinal fluid samples were 14-3-3 – positive and 20 were weakly positive from all 280 samples in total. From the total number (275) of patients, 62 were examined neuropathologically (22%) post mortem. In 25 cases and in six weakly positive cases of 14-3-3 positivity, prion disease of CJD type was proven on autopsy. In other 18 CJD autopsy proved cases, nevertheless, the 14-3-3 protein was evaluated as negative. In two cases of 14-3-3 positivity and in two weakly positive cases a different neuropathological substrate than prion disease was found.

Our results correspond to previously published data, where a predictive value in ß-subunit of protein 14-3-3 detection in CSF is discussed. In comparison to recent publications both sensitivity and specificity of 14-3-3 protein detection for CJD diagnosis is significantly lower in our patient group. This observation can be influenced by our small patient group. Nevertheless, a positive finding of protein 14-3-3 in the cerebrospinal fluid is one of the requirements for CJD diagnosis according to WHO diagnostic criteria. Because of its relatively low specificity it is important to consider the relevance of 14-3-3 positive test in each particular clinical case.

Key words:
14-3-3 protein – prion disease – Creutzfeldt–Jakob disease – neuropathology – diagnostics


1. Dougherty MK, Morrison KD. Unlocking the code of 14-3-3. J Cell Sci 2004; 117(10): 1875–1884.

2. Berg D, Holzmann C, Riess O. 14-3-3 protein in the nervous system. Nat Rev Neurosci 2003; 4(9): 752–762.

3. Hermeking H, Benzinger A. 14-3-3 proteins in cell cycle regulation. Sem Cancer Biol 2006; 16(3): 183–192.

4. Tzivion G, Gupta VS, Kaplun L, Balan V. 14-3-3 proteins as potential oncogenes. Semin Cancer Biol 2006; 16(3): 203–213.

5. World Health Organization. Survillance case definitions for the classification of human transmissible spongiform encephalopathies. In: WHO Manual for Surveillance of Human Transmissible Spongiform Encephalopathies. Geneva: World Health Organization 2003: 71–72.

6. Castellani RJ, Colucci M, Xie Z, Zou W, Li C, Parchi P et al. Sensitivity of 14-3-3 protein test varies in subtypes of sporadic Creutzfeldt-Jakob disease. Neurology 2004; 63(3): 436–442.

7. Cuadrado-Corrales N, Jiménez-Huete A, Albo C, Hortigüela R, Vega L, Cerrato L et al. Impact of the clinical context on the 14-3-3 test for the diagnosis of sporadic CJD. BMC Neurol 2006; 6: 25.

8. Saiz A, Graus F, Dalmau J, Pifarré A, Marin C, Tolosa E. Detection of 14-3-3 brain protein in the cerebrospinal fluid of patients with paraneoplastic neurological disorders. Ann Neurol 1999; 46(5): 774–777.

9. Irani DN, Kerr DA 14-3-3 protein in the cerebrospinal fluid of patients with acute transverse myelitis. Lancet 2000; 355(9207): 901.

10. Hernández Echebarría LE, Saiz A, Graus F, Tejada J, García JM, Clavera B et al. Detection of 14-3-3 protein in the CSF of a patient with Hashimoto‘s encephalopathy. Neurology 2000; 54(7): 1539–1540.

11. Colucci M, Roccatagliata L, Cape­llo E, Narciso E, Latronico N, Tabaton M et al. The 14-3-3 protein in multiple sclerosis: a marker of disease severity. Mult Scler 2004; 10(5): 477–481.

12. Bartosik-Psujek H, Archelos JJ. Tau protein and 14-3-3 are elevated in the cerebrospinal fluid of patients with multiple sclerosis and correlate with intrathecal synthesis of IgG. J Neurol 2004; 251(4): 414–420.

13. Collins SJ, Sanchez-Juan P, Masters CL, Klug GM, van Duijn C, Poleggi A et al. Determinants of diagnostic investigation sensitivities across the clinical spectrum of sporadic Creutzfeldt-Jakob disease. Brain 2006; 129(9): 2278–2287.

14. Sanchez-Juan P, Sánchez-Valle R, Green A, Ladogana A, Cuadrado-Corrales N, Mitrová E et al. Influence of timing on CSF tests value for Creutzfeldt-Jakob disease diagnosis. J Neurol 2007; 254(7): 901–906.

15. Geschwind MD, Martindale J, Miller D, DeArmond SJ, Uyehara‑Lock J, Gaskin D et al. Challenging the clinical utility of the 14-3-3 protein for the diagnosis of sporadic Creutzfeldt-Jakob disease. Arch Neurol 2003; 60(6): 813–816.

16. Gmitterová K, Heinemann U, Bodemer M, Krasnianski A, Meissner B, Kretzschmar HA et al. 14-3-3 CSF levels in sporadic Creutzfeldt-Jakob disease differ across molecular subtypes. Neurobiol Aging. In press 2008.

17. Sanchez-Juan P, Green A, Ladogana A, Cuadrado-Corrales N, Sáanchez-Valle R, Mitrová E et al. CSF tests in the differential diagnosis of Creutzfeldt-Jakob disease. Neurology 2006; 67(4): 637–643.

18. Giraud P, Biacabe AG, Chazot G, Later R, Joyeux O, Moene Y et al. Increased detection of 14-3-3 protein in cerebrospinal fluid in Sporadic Creutzfeldt-Jakob Disease during the disease course. Eur Neurol 2002; 48(4): 218–221.

19. Otto M, Wiltfang J, Cepek L, Neu­mann M, Mollenhauer B, Steinacker P et al. Tau protein and 14-3-3 protein in the differential diagnosis of Creutzfeldt-Jakob disease. Neurology 2002; 58(2): 192–197.

20. Van Everbroeck B, Quoilin S, Boons J, Martin JJ, Cras P. A prospective study of CSF markers in 250 patients with possible Creutzfeldt-Jakob disease. J Neurol Neurosurg Psychiatry 2003; 74(9): 1210–1214.

21. Hort J, Valis M, Waberzinek G, Taláb R, Glossová L, Bojar M et al. Proportion of tau protein to phosphorylated tau protein CSF levels in differential diagnosis of dementia. Nervenarzt 2008; 79(8): 891–898.

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