title: Real time quaking-induced conversion analysis of cerebrospinal fluid in sporadic Creutzfeldt-Jakob disease.
abstract: OBJECTIVE
  Current cerebrospinal fluid (CSF) tests for sporadic Creutzfeldt-Jakob disease (sCJD) are based on the detection of surrogate markers of neuronal damage such as CSF 14-3-3, which are not specific for sCJD. A number of prion protein conversion assays have been developed, including real time quaking-induced conversion (RT-QuIC). The objective of this study is to investigate whether CSF RT-QuIC analysis could be used as a diagnostic test in sCJD.
  
  
  METHODS
  An exploratory study was undertaken that analyzed 108 CSF samples from patients with neuropathologically confirmed sCJD or from control patients. Of the 108 CSF samples, 56 were from sCJD patients (30 female, 26 male; aged 31-84 years; mean age, 62.3 ± 13.5 years), and 52 were from control patients (26 female, 26 male; aged 43-84 years; mean age, 67.8 ± 10.4 years). A confirmatory group of 118 patients was subsequently examined that consisted of 67 cases of neuropathologically confirmed sCJD (33 female, 34 male; aged 39-82 years; mean age, 67.5 ± 9.0 years) and 51 control cases (26 female, 25 male; aged 36-87 years; mean age, 63.5 ± 11.6 years).
  
  
  RESULTS
  The exploratory study showed that RT-QuIC analysis had a sensitivity of 91% and a specificity of 98% for the diagnosis of sCJD. These results were confirmed in the confirmatory study, which showed that CSF RT-QuIC analysis had a sensitivity and specificity of 87% and 100%, respectively.
  
  
  CONCLUSIONS
  This study shows that CSF RT-QuIC analysis has the potential to be a more specific diagnostic test for sCJD than current CSF tests.
authors.affiliation: National Creutzfeldt-Jakob Disease Research & Surveillance Unit, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Lynne I
authors.initials: LI
authors.lastname: McGuire
authors.forename: Alexander H
authors.initials: AH
authors.lastname: Peden
authors.forename: Christina D
authors.initials: CD
authors.lastname: Orrú
authors.forename: Jason M
authors.initials: JM
authors.lastname: Wilham
authors.forename: Nigel E
authors.initials: NE
authors.lastname: Appleford
authors.forename: Gary
authors.initials: G
authors.lastname: Mallinson
authors.forename: Mary
authors.initials: M
authors.lastname: Andrews
authors.forename: Mark W
authors.initials: MW
authors.lastname: Head
authors.forename: Byron
authors.initials: B
authors.lastname: Caughey
authors.forename: Robert G
authors.initials: RG
authors.lastname: Will
authors.forename: Richard S G
authors.initials: RS
authors.lastname: Knight
authors.forename: Alison J E
authors.initials: AJ
authors.lastname: Green
mesh_terms: D048948:14-3-3 Proteins / Q000134:cerebrospinal fluid*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003199:Computer Systems; D007562:Creutzfeldt-Jakob Syndrome / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D006224:Cricetinae; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011328:Prions / Q000134:cerebrospinal fluid*; D012680:Sensitivity and Specificity
chemical_list: D048948:14-3-3 Proteins; D011328:Prions