Development of an ultra-rapid diagnostic method based on heart-type fatty acid binding protein levels in the CSF of CJD patients.
Creutzfeldt-Jakob disease (CJD) is a transmissible, fatal, neurodegenerative disease in humans. Recently, various drugs have been reported to be useful in the treatment of CJD; however, for such treatments to be useful it is essential to rapidly and accurately diagnose CJD. 124 CJD patients and 87 with other diseases causing rapid progressive dementia were examined. Cerebral spinal fluid (CSF) from CJD patients was analyzed by 2D-PAGE and the protein expression pattern was compared with that from healthy subjects. One of three CJD-specific spots was found to be fatty acid binding protein (FABP), and heart-type FABP (H-FABP) was analyzed as a new biochemical marker for CJD. H-FABP ELISA results were compared between CJD patients and patients with other diseases (n = 211). Visual readout accuracy of the Rapicheck(®) H-FABP test panel for CSF was analyzed using an independent measure of CSF H-FABP concentration. The distribution of H-FABP in the brains of CJD patients was examined by immunohistochemistry. ELISA sensitivity and specificity were 90.3% and 92.9%, respectively, and Rapicheck(®) H-FABP sensitivity and specificity were 87.9% and 96.0%, respectively. ELISA and Rapicheck(®) H-FABP assays provided comparable results for 14-3-3 protein and total tau protein. Elevated H-FABP levels were associated with an accumulation of abnormal prion protein, astrocytic gliosis, and neuronal loss in the cerebral cortices of CJD patients. In conclusion, Rapicheck(®) H-FABP of CSF specimens enabled quick and frequent diagnosis of CJD. H-FABP represents a new biomarker for CJD distinct from 14-3-3 protein and total tau protein.
Matsui
Yuki
Y
Faculty of Pharmaceutical Sciences, Department of Pharmaceutical Care and Health Sciences, Fukuoka University, Jonan-ku, Fukuoka, Japan.
Satoh
Katsuya
K
Mutsukura
Kazuo
K
Watanabe
Takuya
T
Nishida
Noriyuki
N
Matsuda
Hideo
H
Sugino
Masaichi
M
Shirabe
Susumu
S
Eguchi
Katsumi
K
Kataoka
Yasufumi
Y
D048948:14-3-3 Proteins / Q000134:cerebrospinal fluid; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001681:Biological Assay / Q000379:methods / Q000592:standards; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D007562:Creutzfeldt-Jakob Syndrome / Q000134:cerebrospinal fluid / Q000175:diagnosis; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay / Q000592:standards; D050556:Fatty Acid-Binding Proteins / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000737:chemistry*; D012680:Sensitivity and Specificity; D016875:tau Proteins / Q000134:cerebrospinal fluid
D048948:14-3-3 Proteins; D015415:Biomarkers; D050556:Fatty Acid-Binding Proteins; D016875:tau Proteins