title: Increased α-synuclein levels in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease.
abstract: Recent studies have shown that cerebrospinal fluid (CSF) levels of α-synuclein (α-syn) are highly elevated in patients with Creutzfeldt-Jakob disease (CJD) compared to controls. However, the diagnostic value of CSF α-syn in CJD has not been established. To confirm whether CSF α-syn is increased in CJD and is a useful marker for this disease, two independent enzyme-linked immunoabsorbent assays (ELISAs) specific for α-syn were used: ELISA 211-FL140, which is specific for full-length α-syn, and ELISA N19-FL140, which is specific for the full-length and associated C-terminal truncated forms of α-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 α-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 α-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 α-syn and t-tau levels may be a useful biomarker for the diagnosis of CJD.
authors.affiliation: Department of Neurology, Research Institute for Geriatrics, Kyoto Prefectural University of Medicine, Kyoto, 602-0841, Japan, kasaita@koto.kpu-m.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kasai
authors.forename: Takahiko
authors.initials: T
authors.lastname: Tokuda
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Ishii
authors.forename: Noriko
authors.initials: N
authors.lastname: Ishigami
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Tsuboi
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Toshiki
authors.initials: T
authors.lastname: Mizuno
authors.forename: Omar M A
authors.initials: OM
authors.lastname: El-Agnaf
mesh_terms: D048948:14-3-3 Proteins / Q000134:cerebrospinal fluid; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D007562:Creutzfeldt-Jakob Syndrome / Q000134:cerebrospinal fluid*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D051844:alpha-Synuclein / Q000134:cerebrospinal fluid*; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D048948:14-3-3 Proteins; D051844:alpha-Synuclein; D016875:tau Proteins
references.citation: Exp Neurol. 2008 Oct;213(2):315-25
references.pmid: 18625222
references.citation: Neuropathol Appl Neurobiol. 2000 Feb;26(1):41-54
references.pmid: 10736066
references.citation: Cell Tissue Res. 2008 Apr;332(1):1-11
references.pmid: 18236081
references.citation: Methods Find Exp Clin Pharmacol. 1998 Apr;20(3):227-35
references.pmid: 9646285
references.citation: Brain. 2010 Mar;133(Pt 3):713-26
references.pmid: 20157014
references.citation: Neurology. 2012 Aug 7;79(6):547-52
references.pmid: 22843257
references.citation: FASEB J. 2003 Oct;17(13):1945-7
references.pmid: 14519670
references.citation: Trends Neurosci. 1991 May;14(5):193-9
references.pmid: 1713721
references.citation: Neurobiol Dis. 2012 Jan;45(1):188-95
references.pmid: 21856424
references.citation: Biochem Biophys Res Commun. 2006 Oct 13;349(1):162-6
references.pmid: 16930553
references.citation: Ann Neurol. 1995 Oct;38(4):643-8
references.pmid: 7574461
references.citation: Dement Geriatr Cogn Disord. 2007;24(3):207-12
references.pmid: 17690553
references.citation: Lancet Neurol. 2011 Mar;10(3):230-40
references.pmid: 21317042
references.citation: Neuroreport. 1993 Jan;4(1):65-8
references.pmid: 8453038
references.citation: Cell Biochem Biophys. 2007;47(2):285-99
references.pmid: 17652776