Journal
JOURNAL OF NEUROLOGY
Volume 261, Issue 6, Pages 1203-1209Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00415-014-7334-7
Keywords
Creutzfeldt-Jakob disease; Cerebrospinal fluid; alpha-Synuclein; Tau; Biomarker; ELISA
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Funding
- Research Committee of CNS Degenerative Disease
- Ministry of Health, Labor, and Welfare of Japan
- Ministry of Education, Culture, Sports, Science and Technology of Japan [23591252, 21790847]
- Michael J. Fox Foundation for Parkinson's Research (NY, USA)
- Grants-in-Aid for Scientific Research [21790847, 23591252] Funding Source: KAKEN
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Recent studies have shown that cerebrospinal fluid (CSF) levels of alpha-synuclein (alpha-syn) are highly elevated in patients with Creutzfeldt-Jakob disease (CJD) compared to controls. However, the diagnostic value of CSF alpha-syn in CJD has not been established. To confirm whether CSF alpha-syn is increased in CJD and is a useful marker for this disease, two independent enzyme-linked immunoabsorbent assays (ELISAs) specific for alpha-syn were used: ELISA 211-FL140, which is specific for full-length alpha-syn, and ELISA N19-FL140, which is specific for the full-length and associated C-terminal truncated forms of alpha-syn. CSF samples from 24 patients with CJD and 24 controls were assessed in this study. We found that samples from the CJD patients showed significantly higher levels of CSF alpha-syn compared to controls in both ELISA (211-FL140 or N19-FL140) tests (P = 0.0467 and P = 0.0010, respectively). However, there was a considerable overlap in the concentration ranges of the two groups of subjects. We also measured the levels of total tau (t-tau) protein in these samples and found that CSF t-tau levels were 5-10-times higher in the CJD group (P < 0.0001) compared with the controls. When the CSF t-tau and alpha-syn levels were combined, the area under the ROC curve (AUC) was slightly increased in clinically diagnosed CJD cases (AUC of 0.964) relative to an AUC of 0.943 for increased CSF t-tau alone. The combined use of CSF alpha-syn and t-tau levels may be a useful biomarker for the diagnosis of CJD.
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