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. INTERPRETATION: This study shows that CSF RT-QuIC analysis has the potential to be a more specific diagnostic test for sCJD than current CSF tests.
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. INTERPRETATION: 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: Ryuichiro Atarashi; Jason M Wilham; Leah Christensen; Andrew G Hughson; Roger A Moore; Lisa M Johnson; Henry A Onwubiko; Suzette A Priola; Byron Caughey Journal: Nat Methods Date: 2008-03 Impact factor: 28.547
Authors: P Sanchez-Juan; A Green; A Ladogana; N Cuadrado-Corrales; R Sáanchez-Valle; E Mitrováa; K Stoeck; T Sklaviadis; J Kulczycki; K Hess; M Bodemer; D Slivarichová; A Saiz; M Calero; L Ingrosso; R Knight; A C J W Janssens; C M van Duijn; I Zerr Journal: Neurology Date: 2006-08-22 Impact factor: 9.910
Authors: Christina D Orrú; Jason M Wilham; Andrew G Hughson; Lynne D Raymond; Kristin L McNally; Alex Bossers; Ciriaco Ligios; Byron Caughey Journal: Protein Eng Des Sel Date: 2009-07-01 Impact factor: 1.650
Authors: Andrew F Hill; Susan Joiner; Jonathan D F Wadsworth; Katie C L Sidle; Jeanne E Bell; Herbert Budka; James W Ironside; John Collinge Journal: Brain Date: 2003-06 Impact factor: 13.501
Authors: Michael D Geschwind; Jennifer Martindale; Deborah Miller; Stephen J DeArmond; Jane Uyehara-Lock; David Gaskin; Joel H Kramer; Nicholas M Barbaro; Bruce L Miller Journal: Arch Neurol Date: 2003-06
Authors: I Zerr; K Kallenberg; D M Summers; C Romero; A Taratuto; U Heinemann; M Breithaupt; D Varges; B Meissner; A Ladogana; M Schuur; S Haik; S J Collins; Gerard H Jansen; G B Stokin; J Pimentel; E Hewer; D Collie; P Smith; H Roberts; J P Brandel; C van Duijn; M Pocchiari; C Begue; P Cras; R G Will; P Sanchez-Juan Journal: Brain Date: 2009-09-22 Impact factor: 13.501
Authors: Sonia M Vallabh; Chloe K Nobuhara; Franc Llorens; Inga Zerr; Piero Parchi; Sabina Capellari; Eric Kuhn; Jacob Klickstein; Jiri G Safar; Flavia C Nery; Kathryn J Swoboda; Michael D Geschwind; Henrik Zetterberg; Steven E Arnold; Eric Vallabh Minikel; Stuart L Schreiber Journal: Proc Natl Acad Sci U S A Date: 2019-04-01 Impact factor: 11.205
Authors: Eri Saijo; Michael A Metrick; Shunsuke Koga; Piero Parchi; Irene Litvan; Salvatore Spina; Adam Boxer; Julio C Rojas; Douglas Galasko; Allison Kraus; Marcello Rossi; Kathy Newell; Gianluigi Zanusso; Lea T Grinberg; William W Seeley; Bernardino Ghetti; Dennis W Dickson; Byron Caughey Journal: Acta Neuropathol Date: 2019-10-16 Impact factor: 17.088
Authors: Davin M Henderson; Joanne M Tennant; Nicholas J Haley; Nathaniel D Denkers; Candace K Mathiason; Edward A Hoover Journal: J Gen Virol Date: 2017-07-13 Impact factor: 3.891
Authors: Christina D Orrú; Matilde Bongianni; Giovanni Tonoli; Sergio Ferrari; Andrew G Hughson; Bradley R Groveman; Michele Fiorini; Maurizio Pocchiari; Salvatore Monaco; Byron Caughey; Gianluigi Zanusso Journal: N Engl J Med Date: 2014-08-07 Impact factor: 91.245