Creutzfeldt-Jakob disease is a rare, but rapidly progressive, up to now untreatable and fatal neurodegenerative disorder. Clinical diagnosis of Creutzfeldt-Jakob disease (CJD) is difficult; however, it can be facilitated by suitable biomarkers. Aim of the present study is to compare levels of cerebrospinal fluid biomarkers (total tau protein, phosphorylated-tau protein, protein 14-3-3 and amyloid beta) in Slovak population of CJD suspect cases, retrospectively in over a 10-year period. One thousand three hundred sixty-four CSF samples from patients with suspect CJD, forming a homogenous group in terms of geographical as well as of equal transport conditions, storage and laboratory processing, were analysed. Definite diagnosis of Creutzfeldt-Jakob disease was confirmed in 101 patients with genetic form, and 60 patients with its sporadic form of the disease. Specificity of protein 14-3-3 and total tau in both forms CJD was similar (87 % for P14-3-3/85 % for total tau), sensitivity to P 14-3-3 and total tau was higher in sporadic Creutzfeldt-Jakob disease (sCJD) (90/95 %) than in genetic Creutzfeldt-Jakob disease (gCJD) (89/74 %). As expected, the total tau levels were significantly higher in CJD patients than in controls, but there was also significant difference between gCJD and sCJD (levels in gCJD were lower; p = 0.003). There was no significant difference in p-tau and Aβ 1-42 levels neither between both CJD forms nor between CJD patients and control group.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Prusiner SB (1982) Novel proteinaceous infectious particles cause scrapie. Science 216:136–144
Mitrová E (1991) Some new aspects of CJD epidemiology in Slovakia. Eur J Epidem 7(5):439–449
Mitrová E, Belay G (2002) Creutzfeldt-Jakob disease with E200K mutation in Slovakia: characterization and development. Acta Virol 46:31–39
Korczyn AD (1994) Neurologic genetic diseases of Jewish people. Biomed Pharmacother 48:391–397
Meiner Z, Kahana E, Baitcher F, Korczyn AD, Chapman J, Cohen OS, Milo R, Aharon-Perez J et al (2011) Tau and 14-3-3 of genetic and sporadic Creutzfeldt-Jakob disease patients in Israel. J Neurol 258:255–262
WHO (2003) WHO manual for surveillance of human transmissible spongiform encephalopathies, including variant Creutzfeldt-Jakob disease, Geneva ISBN 92–4–154588-7
Zerr I, Pocchiari M, Collins S, Brandel JP, de Pedro Cuesta J, Knight RSG, Bernheimer H, Cardone F et al (2000) Analysis of EEG and CSF 14-3-3 proteins as aids to the diagnosis of Creutzfeldt-Jakob disease. Neurology 55:811–815
Zerr I, Kallenberg K, Summers DM, Romero C, Taratuto A, Ladogana A, Schuur M, Haik S et al (2009) Updated clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease. Brain 132:2659–2668
Collins SJ, Sanchez-Juan P, Masters CL, Klug GM, van Duijn C, Poleggi A, Pocchiari M, Almonti S et al (2006) Determinatinants of diagnostic investigation sensitivities across the clinical spectrum of sporadic CJD. Brain 129:2278–2287
Schmitz M, Ebert E, Stoeck K, Karch A, Collins S, Calero M, Sklaviadis T, Laplanche JL et al (2016) Validation of 14-3-3 protein as a marker in sporadic Creutzfeldt-Jakob disease diagnostic. Mol Neurobiol 53(4):2189–2199
Stoeck K, Sanchez-Juan P, Gawinecka J, Green A, Ladogana A, Pocchiari M, Sanchez-Valle R, Mitrova E et al (2012) Cerebrospinal fluid biomarker supported diagnosis of Creutzfeldt-Jakob disease and rapid dementias: a longitudinal multicentre study over 10 years. Brain 135:3051–3061
Chohan G, Pennigton C, Mackenzie J, Andrews M, Everington D, Will R, Knight R, Green A (2010) The role of cerebrospinal fluid 14-3-3 and other proteins in the diagnosis of sporadic Creutzfeldt-Jakob disease in the UK: a 10-year review. J Neurol Neurosurg Psychiatry 81:1243–1248
Kapaki E, Kilidireas K, Paraskevas GP, Michalopoulou M, Patsouris E (2001) Highly increased CSF tau-protein and decreased beta-amyloid (1-42) in sporadic CJD: discrimination from Alzheimer’s disease? J Neurol Neurosurg Psychiatry 71(3):401–403
Otto M, Wiltfang J, Tumani H, Zerr I, Lantsch M, Kornhuber J, Weber T, Kretzschmar HA et al (1997) Elevated levels of tau-protein in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease. Neurosci Lett 225(3):210–212
Small DH, McLean CA (1999) Alzheimer’s disease and the amyloid beta protein: what is the role of amyloid? J Neurochem 73(2):443–449
Coulthart MB, Jansen GH, Olsen E, Godal DL, Connolly T, Choi BC, Wang Z, Cashman NR (2011) Diagnostic accuracy of cerebrospinal fluid protein markers for sporadic Creutzfeldt-Jakob disease in Canada: a 6-year prospective study. BMC Neurol 11:133
Zerr I, Bodemer M, Gefeller O, Otto M, Poser S, Wiltfang J, Windl O, Kretschmar HA et al (1998) Detection of 14-3-3 protein in the cerebrospinal fluid supports the diagnosis of Creutzfeldt-Jakob disease. Ann Neurol 43:32–40
Otto M, Wiltfang J, Cepek L et al (2002) Tau protein and 14-3-3 in the differential diagnosis of Creutzfeldt-Jakob disease. Neurology 58:192–197
Sanchez-Juan P, Green A, Ladogana A, Cuadrado-Corrales N, Sanchez-Valle R, Mitrova E, Stoeck K, Sklaviadis T et al (2006) CSF tests in the differential diagnosis of Creutzfeldt-Jakob disease. Neurology 67:637–643
Palmer MS, Dryden AJ, Hughes JT, Collinge J (1991) Homozygous prion protein genotype predisposes to sporadic Creutzfeldt-Jakob disease. Nature 352:340–342
Ladogana A, Sanchez Juan P, Mitrova E, Green A, Cuadrado-Corrales N, Sanchez-Valle R, Koscova S, Aguzzi A et al (2009) Cerebrospinal fluid biomarkers in human genetic transmissible spongiform encephalopathies. J Neurol 256:1620–1628
Skinningsrud A, Stenser V, Gundersen AS, Fladby T (2008) Cerebrospinal fluid markers in Creutzfeldt-Jakob disease. Cerebrospinal Fluid Res 5
Baldeiras IE, Ribeiro MH, Pacheco P, Machado A, Santana I, Cunha L, Oliveira C (2009) Diagnostic value of CSF protein profile in a Portuguese population of sCJD patients. J Neurol 256:1540–1550
Sanchez-Juan P, Sanchez-Valle R, Green A, Ladogana A, Cuadrado-Corrales N, Mitrova E, Stoeck K, Sklaviadis T et al (2007) Influence of timing on CSF tests value for Creutzfeldt-Jakob disease diagnosis. J Neurol 254(7):901–906
Cohen OS, Chapman J, Korczyn AD, Warman-Alaluf N, Nitsan Z, Appel S, Kahana E, Rosenmann H (2015) CSF tau correlates with CJD severity and cognitive decline. Acta Neurol Scand . doi:10.1111/ane.12441May 25
Hainfeller JA, Wanschitz J, Jellinger K, Liberski PP, Gullotta F, Budka H (1998) Coexistence of Alzheimer-type neuropathology in Creutzfeldt-Jakob disease. Acta Neuropathol 96:116–122
Krasnianski A, Heinemann U, Ponto C, Kortt J, Kallenberg K, Varges D, Schulz-Schaeffer WJ, Kretzschmar HA et al (2016) Clinical findings and diagnosis in genetic prion disease in Germany. Eur J Epidemiol 31(2):187–196
Satoh K, Shirabe S, Eguchi H, Tsujino A, Eguchi K, Tsujihata M, Niwa M, Katamine S et al (2006) 14-3-3 protein, total tau and phosphorylated tau in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease and neurodegenerative disease in Japan. Cell Mol Neurobiol 26:45–52
Noguchi-Shinohara M, Hamaguchi T, Nozaki I, Sakai K, Yamada M (2011) Serum tau protein as a marker for the diagnosis of Creutzfeldt-Jakob disease. J Neurol 258:1464–1468
Otto M, Esselmann H, Schulz-Schaeffer W, Neumann N, Schröter A, Ratzka P, Cepek L, Zerr I et al (2000) Decreased β-amyloid 1-42 in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease. Neurology 54:1099–1102
Alcolea D, Martínez-Lage P, Sánchez-Juan P, Olazarán J, Antúnez C, Izagirre A, Ecay-Torres M, Estanga A et al (2015) Amyloid precursor protein metabolism and inflammation markers in preclinical Alzheimer disease. Neurology 85(7):626–633
Zanusso G, Fiorini M, Ferrari S, Gajofatto A, Cagnin A, Galassi A, Richelli S, Monaco S (2011) Cerebrospinal fluid markers in sporadic Creutzfeldt-Jakob disease. Int J Mol Sci 12:6281–6292
Llorens F, Schmitz M, Karch A, Cramm M, Lange P, Gherib K, Varges D, Schmidt C et al (2016) Comparative analysis of cerebrospinal fluid biomarkers in the differential diagnosis of neurodegenerative dementia. Alzheimers Dement 12(5):577–589
The study was supported by grant from EU Joint Program-Neurodegenerative Disease Research (JPND-DEMTEST Biomarker based diagnosis of rapid progressive dementias-optimization of diagnostic protocols, 01ED1201A) and by Center of Excellence in Environmental Health, ITMS No.26240120033, based on the supporting operational Research and development program financed from the European Regional Development Fund.
Thanks to Dana Vajcikova for technical assistance.
Conflict of Interests
The authors declare that they have no conflicts of interests.
Koscova S. and Slivarichova-Zakova Dana contributed equally
About this article
Cite this article
Koscova, S., Zakova Slivarichova, D., Tomeckova, I. et al. Cerebrospinal Fluid Biomarkers in the Diagnosis of Creutzfeldt-Jakob Disease in Slovak Patients: over 10-Year Period Review. Mol Neurobiol 54, 5919–5927 (2017). https://doi.org/10.1007/s12035-016-0128-4
- Cerebrospinal fluid
- Creutzfeldt-Jakob disease
- E200K mutation
- Protein 14-3-3
- Total tau