High Diagnostic Accuracy of RT-QuIC Assay in a Prospective Study of Patients with Suspected sCJD.
14-3-3 Proteins
/ cerebrospinal fluid
Aged
Aged, 80 and over
Biomarkers
/ analysis
Creutzfeldt-Jakob Syndrome
/ diagnostic imaging
Electroencephalography
Female
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Olfactory Mucosa
Prions
/ genetics
Prospective Studies
Sensitivity and Specificity
tau Proteins
/ cerebrospinal fluid
CSF
RT-QuIC
biomarkers
prion
rapidly progressive dementia
sCJD
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
30 Jan 2020
30 Jan 2020
Historique:
received:
24
12
2019
revised:
26
01
2020
accepted:
27
01
2020
entrez:
6
2
2020
pubmed:
6
2
2020
medline:
11
11
2020
Statut:
epublish
Résumé
The early and accurate in vivo diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) is essential in order to differentiate CJD from treatable rapidly progressive dementias. Diagnostic investigations supportive of clinical CJD diagnosis include magnetic resonance imaging (MRI), electroencephalogram (EEG), 14-3-3 protein detection, and/or real-time quaking-induced conversion (RT-QuIC) assay positivity in the cerebrospinal fluid (CSF) or in other tissues. The total CSF tau protein concentration has also been used in a clinical setting for improving the CJD diagnostic sensitivity and specificity. We analyzed 182 CSF samples and 42 olfactory mucosa (OM) brushings from patients suspected of having sCJD with rapidly progressive dementia (RPD), in order to determine the diagnostic accuracy of 14-3-3, the total tau protein, and the RT-QuIC assay. A probable and definite sCJD diagnosis was assessed in 102 patients. The RT-QuIC assay on the CSF samples showed a 100% specificity and a 96% sensitivity, significantly higher compared with 14-3-3 (84% sensitivity and 46% specificity) and tau (85% sensitivity and 70% specificity); however, the combination of RT-QuIC testing of the CSF and OM samples resulted in 100% sensitivity and specificity, proving a significantly higher accuracy of RT-QuIC compared with the surrogate biomarkers in the diagnostic setting of patients with RPD. Moreover, we showed that CSF blood contamination or high protein levels might interfere with RT-QuIC seeding. In conclusion, we provided further evidence that the inclusion of an RT-QuIC assay of the CSF and OM in the diagnostic criteria for sCJD has radically changed the clinical approach towards the diagnosis.
Identifiants
pubmed: 32019068
pii: ijms21030880
doi: 10.3390/ijms21030880
pmc: PMC7038328
pii:
doi:
Substances chimiques
14-3-3 Proteins
0
Biomarkers
0
Prions
0
tau Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : BRAIN RESEARCH FOUNDATION VERONA ONLUS
ID : 2017 II
Organisme : Associazione Luca Nuti
ID : /
Organisme : CJD Foundation
ID : /
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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