Alternative application of Tau protein in Creutzfeldt-Jakob disease diagnosis: Improvement for weakly positive 14-3-3 protein in the laboratory.
The 14-3-3 protein has been used as a biomarker for the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD). However, weakly positive 14-3-3 leads to false positive results and an incorrect diagnosis. We attempted to use quantitative data for tau protein to provide an accurate diagnosis based on weak 14-3-3 protein. Sixty-two patients with sCJD, including pathologically confirmed, clinically definite, and probable cases, and 89 non-CJD patients were investigated based on a Korean population. Among them, 20 sCJD and 14 non-CJD showed weakly positive 14-3-3. The total tau (t-tau) and phosphorylated tau (p-tau) protein levels were measured by ELISA, and the p-tau to t-tau ratio (p/t ratio) was calculated. The combined use of the 14-3-3 protein assay, t-tau levels, and p/t ratio improved the specificity of diagnosis compared with the use of the 14-3-3 protein assay alone (47% for 14-3-3 alone; 85.94% for 14-3-3 combined with t-tau; 90.62% for 14-3-3 combined with the p/t ratio). In addition, 18 of 20 sCJD and 12 of 14 non-CJD who were weakly positive for 14-3-3 were positive for the p/t ratio and negative for the p/t ratio, respectively. When used in combination with the 14-3-3 protein, the tau protein is useful as a biomarker for the precise diagnosis of sCJD.
Division of Zoonoses, Center for Immunology &Pathology, National Institute of Health, Korea Centers for Disease Control and Prevention, Chungcheongbuk-do 28159, Korea.
Jae Wook
JW
Hyeon
Division of Zoonoses, Center for Immunology &Pathology, National Institute of Health, Korea Centers for Disease Control and Prevention, Chungcheongbuk-do 28159, Korea.
Su Yeon
SY
Kim
Division of Zoonoses, Center for Immunology &Pathology, National Institute of Health, Korea Centers for Disease Control and Prevention, Chungcheongbuk-do 28159, Korea.
Jeongmin
J
Lee
Division of Zoonoses, Center for Immunology &Pathology, National Institute of Health, Korea Centers for Disease Control and Prevention, Chungcheongbuk-do 28159, Korea.
Jun Sun
JS
Park
Division of Zoonoses, Center for Immunology &Pathology, National Institute of Health, Korea Centers for Disease Control and Prevention, Chungcheongbuk-do 28159, Korea.
Kyu Jam
KJ
Hwang
Division of Zoonoses, Center for Immunology &Pathology, National Institute of Health, Korea Centers for Disease Control and Prevention, Chungcheongbuk-do 28159, Korea.
Sol Moe
SM
Lee
Gachon BioNano Research Institute, Gachon University, Gyeonggi-do 461-701, Korea.
SeongSoo A
SA
An
College of Pharmacy, Chungbuk National University, Cheongju 361-763, Korea.
Myung Koo
MK
Lee
Division of Zoonoses, Center for Immunology &Pathology, National Institute of Health, Korea Centers for Disease Control and Prevention, Chungcheongbuk-do 28159, Korea.
Young Ran
YR
Ju
D048948:14-3-3 Proteins / Q000134:cerebrospinal fluid*; D000368:Aged; D044466:Asian People; D015415:Biomarkers; D007562:Creutzfeldt-Jakob Syndrome / Q000175:diagnosis* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D012680:Sensitivity and Specificity; D016875:tau Proteins / Q000134:cerebrospinal fluid / Q000378:metabolism*
D048948:14-3-3 Proteins; D015415:Biomarkers; D016875:tau Proteins