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Multicenter Study
. 2025 Feb 11;272(3):198.
doi: 10.1007/s00415-024-12757-8.

Isolated CSF RT-QuIC positivity associates with a less aggressive disease course and decreased levels of neuronal/glial damage biomarkers in patients with sporadic Creutzfeldt-Jakob disease

Laura Naranjo  1 , Jordi Sarto  2 , Carlos Nos  3 , Daniel Alcolea  4 , Iñigo Rodríguez-Baz  4 , Irene Navalpotro-Gómez  5 , Aída Fernández-Lebrero  5 , Bernat Bertrán-Recasens  6 , María Elena Erro  7 , Ana Lara Pelayo-Negro  8 , Clara Esteve  9 , Susana Fernández  10 , Andreu Massot-Tarrús  11 , Anuncia Boltes  12 , Albert Torrents  13 , Nicolau Guanyabens  14 , Alfredo Palomino-García  15 , Natalia Egri  1 , Albert Lladó  2 , Mircea Balasa  2 , María Antonia Romera  1 , María Del Carmen Antón  1 , Rocío Soledad Couso  1 , Raquel Sánchez-Valle #  16 , Raquel Ruiz-García #  17 ; Spanish sCJD Study Group
Collaborators, Affiliations
Multicenter Study

Isolated CSF RT-QuIC positivity associates with a less aggressive disease course and decreased levels of neuronal/glial damage biomarkers in patients with sporadic Creutzfeldt-Jakob disease

Laura Naranjo et al. J Neurol. .

Abstract

Discrepancies in results between cerebrospinal fluid (CSF) 14-3-3 protein and prion protein detection using real-time quaking-induced conversion (RT-QuIC) might limit the confidence in ante-mortem clinical diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD). We aimed to evaluate the concordance and diagnostic performance of 14-3-3 protein and RT-QuIC in a real clinical practice cohort, and to analyze neuronal/glial damage biomarkers in sCJD patients based on their diagnostic assay results. A retrospective multicentre study was conducted on 157 suspected sCJD patients from 38 Spanish hospitals in a 4-year period. CSF 14-3-3 protein and RT-QuIC were simultaneously evaluated in a single laboratory. A diagnosis of probable sCJD was established in 63 patients (40.1%), of which 12 (19.0%) were ultimately diagnosed with definite sCJD. Forty-one sCJD patients (65.1%) were positive for both 14-3-3 protein and RT-QuIC, 17 (27.0%) isolated positive for RT-QuIC, and 5 (7.9%) isolated positive for 14-3-3 protein. RT-QuIC demonstrated higher sensitivity (92.1%) and specificity (98.9%) compared to 14-3-3 (73.0% and 62.8%) for the diagnosis of sCJD. Isolated RT-QuIC positivity was associated with longer disease duration (median: 10.5 months, IQR: 8.8-15.7), higher frequency of Met/Val cases (75.0%), lower prevalence of periodic sharp-wave complexes (5.9%), and lower levels of GFAP (3967.4 pg/mL), UCH-L1 (2218.1 pg/mL), and t-Tau (228.8 pg/mL) compared to double-positive and isolated 14-3-3-positive patients. In conclusion, CSF RT-QuIC is a highly specific and sensitive biomarker for ante-mortem sCJD diagnosis and should be considered as the preferred CSF ancillary test. Isolated RT-QuIC positivity indicates a less aggressive biological disease in sCJD patients.

Keywords: 14-3-3 protein; Diagnostic performance; Neuronal/glial damage biomarkers; Real-time quaking-induced conversion; Sporadic Creutzfeldt–Jakob disease.

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Conflict of interest statement

Declarations. Conflicts of interest: RSV has served in Advisory boards Meetings for Wave Life Sciences, Ionis, UCB, Prevail, Pfzer and Novo Nordisk and received personal fees for participating in educational activities from Roche Diagnostics and Neuraxpharm. The other authors declare no conflict of interest. Ethics approval: This study was performed in accordance with the Ethical Principles for Medical Research of the Declaration of Helsinki and was approved by the Clinical Research Ethics Committee of Hospital Clinic de Barcelona (HCB/2022/0603).

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