Challenging the clinical utility of the 14-3-3 protein for the diagnosis of sporadic Creutzfeldt-Jakob disease

Arch Neurol. 2003 Jun;60(6):813-6. doi: 10.1001/archneur.60.6.813.

Abstract

Background: Creutzfeldt-Jakob disease (CJD) is a rapidly progressive and fatal neurodegenerative disorder for which there is no noninvasive and disease-specific test for premortem diagnosis. Previous studies have suggested that, in the proper clinical context, the 14-3-3 protein in cerebrospinal fluid is a reliable marker for sporadic CJD.

Objective: To assess the sensitivity of the cerebrospinal fluid 14-3-3 protein test among patients with definite sporadic CJD.

Design and setting: We reviewed cases of sporadic CJD referred to our institution that were ultimately proved by pathological examination and on which cerebrospinal fluid 14-3-3 testing had been performed.

Participants: Patients with CJD referred to our institution for clinical and/or pathological evaluation (biopsy- or autopsy-confirmed diagnosis) from January 1, 1998, through July 15, 2002, and on whom 14-3-3 testing had been performed. Thirty-two such patients with definite sporadic CJD were identified. Main Outcome Measure The 14-3-3 test results, from various laboratories, in these 32 patients.

Results: Seventeen of the 32 patients had a positive result for the 14-3-3 test, yielding a sensitivity of only 53%. A positive 14-3-3 result was significantly correlated with a shorter time between disease onset and the lumbar puncture for the 14-3-3 test.

Conclusions: Testing for the 14-3-3 protein is only modestly sensitive to sporadic CJD, and we caution against ruling out a diagnosis of the disease on the basis of a negative 14-3-3 result.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 14-3-3 Proteins
  • Adult
  • Aged
  • Biomarkers
  • Clinical Laboratory Techniques / standards
  • Creutzfeldt-Jakob Syndrome / cerebrospinal fluid*
  • Creutzfeldt-Jakob Syndrome / diagnosis*
  • Creutzfeldt-Jakob Syndrome / pathology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunoblotting
  • Male
  • Middle Aged
  • Reference Standards
  • Tyrosine 3-Monooxygenase / cerebrospinal fluid*
  • United States

Substances

  • 14-3-3 Proteins
  • Biomarkers
  • Tyrosine 3-Monooxygenase