Skip to main content

Advertisement

SpringerLink
Log in

A systematic review comparing the diagnostic value of 14-3-3 protein in the cerebrospinal fluid, RT-QuIC and RT-QuIC on nasal brushing in sporadic Creutzfeldt–Jakob disease

  • Review
  • Published:
Acta Neurologica Belgica Aims and scope Submit manuscript

Abstract

Background

Sporadic Creutzfeldt–Jakob disease (sCJD) is a human prion disease that is a relatively common differential diagnosis in dementia patients. Therefore it needs a good diagnostic tool. Brain autopsy is the golden standard for the diagnosis of CJD; however, a less invasive technique is 14-3-3 protein measurement in the cerebrospinal fluid (CSF). In this systematic review, we compared the diagnostic value of the 14-3-3 protein measurement to the newer RT-QuIC test and a variant of RT-QuIC where nasal brushing is used to collect the samples.

Methods

The search via MeSH terms and quality assessment was carried out by two individual researchers.

Results

In 14-3-3 and RT-QuIC the sensitivity was comparable, respectively, 88% and 86%. Specificity however was higher in RT-QuIC 99.5% compared to 80% in 14-3-3. Nasal brushing showed the best results with a sensitivity of 97% and a specificity of 100%.

Conclusion

Nasal brushing, despite being the best diagnostic tool according to the data, needs more study since there has only been a few studies regarding the technique. It is safe to say that due to the high specificity, RT-QuIC is superior to 14-3-3 testing.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Poggiolini I, Saverioni D, Parchi P (2013) Prion protein misfolding, strains, and neurotoxicity: an update from studies on mammalian prions. Int J Cell Biol 2013:1–24. https://doi.org/10.1155/2013/910314

    Article  CAS  Google Scholar 

  2. Creutzfeldt–Jakob disease (CJD) and variant CJD (vCJD)

  3. Robinson R (2011) MRI can distinguish CJD from other rapid dementias. Neurol Today 11(9)

  4. Orrú CD, Bongianni M, Tonoli G, Ferrari S, Hughson AG, Groveman BR et al (2014) A Test for Creutzfeldt–Jakob Disease Using Nasal Brushings. N Engl J Med 371(6):519–529

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. McGuire LI, Peden AH, Orru CD, Wilham JM, Appleford NE, Mallinson G et al (2012) Real time quaking-induced conversion analysis of cerebrospinal fluid in sporadic Creutzfeldt–Jakob disease. Ann Neurol 72(2):278–285

    Article  PubMed  PubMed Central  Google Scholar 

  6. Iacono D, Ferrari S, Gelati M, Zanusso G, Mariotto S, Monaco S (2015) Sporadic Creutzfeldt–Jakob disease: prion pathology in medulla oblongata-possible routes of infection and host susceptibility. Biomed Res Int 2015:396791

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Orru CD, Bongianni M, Tonoli G, Ferrari S, Hughson AG, Groveman BR et al (2014) A test for Creutzfeldt–Jakob disease using nasal brushings. N Engl J Med 371(6):519–529

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Atarashi R, Sano K, Satoh K, Nishida N (2011) Real-time quaking-induced conversion: a highly sensitive assay for prion detection. Prion 5(3):150–153

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Atarashi R, Satoh K, Sano K, Fuse T, Yamaguchi N, Ishibashi D et al (2011) Ultrasensitive human prion detection in cerebrospinal fluid by real-time quaking-induced conversion. Nat Med 17(2):175–178

    Article  PubMed  CAS  Google Scholar 

  10. Bahl JM, Heegaard NH, Falkenhorst G, Laursen H, Hogenhaven H, Molbak K et al (2009) The diagnostic efficiency of biomarkers in sporadic Creutzfeldt–Jakob disease compared to Alzheimer’s disease. Neurobiol Aging 30(11):1834–1841

    Article  PubMed  CAS  Google Scholar 

  11. Baldeiras IE, Ribeiro MH, Pacheco P, Machado A, Santana I, Cunha L et al (2009) Diagnostic value of CSF protein profile in a Portuguese population of sCJD patients. J Neurol 256(9):1540–1550

    Article  PubMed  Google Scholar 

  12. Collins S, Boyd A, Fletcher A, Gonzales M, McLean CA, Byron K et al (2000) Creutzfeldt–Jakob disease: diagnostic utility of 14-3-3 protein immunodetection in cerebrospinal fluid. J Clin Neurosci 7(3):203–208

    Article  PubMed  CAS  Google Scholar 

  13. Coulthart MB, Jansen GH, Olsen E, Godal DL, Connolly T, Choi BC et al (2011) Diagnostic accuracy of cerebrospinal fluid protein markers for sporadic Creutzfeldt–Jakob disease in Canada: a 6-year prospective study. BMC Neurol 11:133

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Cramm M, Schmitz M, Karch A, Mitrova E, Kuhn F, Schroeder B et al (2015) Stability and reproducibility underscore utility of RT-QuIC for diagnosis of Creutzfeldt–Jakob disease. Mol Neurobiol

  15. Forner SA, Takada LT, Bettcher BM, Lobach IV, Tartaglia MC, Torres-Chae C et al (2015) Comparing CSF biomarkers and brain MRI in the diagnosis of sporadic Creutzfeldt–Jakob disease. Neurol Clin Pract 5(2):116–125

    Article  PubMed  PubMed Central  Google Scholar 

  16. Green AJ, Ramljak S, Muller WE, Knight RS, Schroder HC (2002) 14-3-3 in the cerebrospinal fluid of patients with variant and sporadic Creutzfeldt–Jakob disease measured using capture assay able to detect low levels of 14-3-3 protein. Neurosci Lett 324(1):57–60

    Article  PubMed  CAS  Google Scholar 

  17. Matsui Y, Satoh K, Miyazaki T, Shirabe S, Atarashi R, Mutsukura K et al (2011) High sensitivity of an ELISA kit for detection of the gamma-isoform of 14-3-3 proteins: usefulness in laboratory diagnosis of human prion disease. BMC Neurol 11:120-

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. McGuire LI, Peden AH, Orrú CD, Wilham JM, Appleford NE, Mallinson G et al (2012) RT-QuIC analysis of cerebrospinal fluid in sporadic Creutzfeldt–Jakob disease. Ann Neurol 72(2):278–285

    Article  PubMed  PubMed Central  Google Scholar 

  19. Orrú CD, Groveman BR, Hughson AG, Zanusso G, Coulthart MB, Caughey B (2015) Rapid and sensitive RT-QuIC detection of human Creutzfeldt–Jakob disease using cerebrospinal fluid. mBio 6(1):e02451–e02414

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Pennington C, Chohan G, Mackenzie J, Andrews M, Will R, Knight R et al (2009) The role of cerebrospinal fluid proteins as early diagnostic markers for sporadic Creutzfeldt–Jakob disease. Neurosci Lett 455(1):56–59

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  22. Van Everbroeck B, Green AJ, Vanmechelen E, Vanderstichele H, Pals P, Sanchez-Valle R et al (2002) Phosphorylated tau in cerebrospinal fluid as a marker for Creutzfeldt–Jakob disease. J Neurol Neurosurg Psychiatry 73(1):79–81

    Article  PubMed  PubMed Central  Google Scholar 

  23. Koscova S, Zakova Slivarichova D, Tomeckova I, Melicherova K, Stelzer M, Janakova A et al (2016) Cerebrospinal Fluid Biomarkers in the Diagnosis of Creutzfeldt–Jakob Disease in Slovak Patients: over 10-Year Period Review. Molecular neurobiology

  24. Bongianni M, Orru C, Groveman BR, Sacchetto L, Fiorini M, Tonoli G et al (2017) Diagnosis of human prion disease using real-time quaking-induced conversion testing of olfactory mucosa and cerebrospinal fluid samples. JAMA neurology 74(2):155–162

    Article  PubMed  Google Scholar 

  25. Groveman BR, Orrú CD, Hughson AG, Bongianni M, Fiorini M, Imperiale D et al (2017) Extended and direct evaluation of RT-QuIC assays for Creutzfeldt–Jakob disease diagnosis. Ann Clin Transl Neurol 4(2):139–144

    Article  PubMed  CAS  Google Scholar 

Download references

Funding

No financial support was offered nor accepted for this systematic review.

Author information

Authors and Affiliations

  1. Faculty of Medicine and Health Sciences, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, Belgium

    Olivia Behaeghe & Elias Mangelschots

  2. Laboratory of Neurology, Translational Neurosciences, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, Belgium

    Bart De Vil & Patrick Cras

  3. Institute Born-Bunge, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, Belgium

    Bart De Vil & Patrick Cras

  4. Department of Neurology, Antwerp University Hospital, Wilrijkstraat 10, 2650, Edegem, Belgium

    Patrick Cras

Authors
  1. Olivia Behaeghe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elias Mangelschots
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bart De Vil
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Patrick Cras
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Olivia Behaeghe.

Ethics declarations

Conflict of interest

A possible conflict of interest is that one of the authors is now editor-in-chief of this journal (Patrick Cras, PhD, MD).

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

An informed consent was not needed here, as this is a systematic review.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Behaeghe, O., Mangelschots, E., De Vil, B. et al. A systematic review comparing the diagnostic value of 14-3-3 protein in the cerebrospinal fluid, RT-QuIC and RT-QuIC on nasal brushing in sporadic Creutzfeldt–Jakob disease. Acta Neurol Belg 118, 395–403 (2018). https://doi.org/10.1007/s13760-018-0995-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13760-018-0995-8

Keywords

Search

Navigation