Diagnostic and prognostic value of cerebrospinal fluid SNAP-25 and neurogranin in Creutzfeldt-Jakob disease in a clinical setting cohort of rapidly progressive dementias

Background The levels of synaptic markers synaptosomal-associated protein 25 (SNAP-25) and neurogranin (Ng) have been shown to increase early in the cerebrospinal fluid (CSF) of patients with Creutzfeldt-Jakob disease (CJD) and to have prognostic potential. However, no validation studies assessed th...
Ausführliche Beschreibung

Background The levels of synaptic markers synaptosomal-associated protein 25 (SNAP-25) and neurogranin (Ng) have been shown to increase early in the cerebrospinal fluid (CSF) of patients with Creutzfeldt-Jakob disease (CJD) and to have prognostic potential. However, no validation studies assessed these biomarkers' diagnostic and prognostic value in a large clinical setting cohort of rapidly progressive dementia. Methods In this retrospective study, using commercially available immunoassays, we measured the levels of SNAP-25, Ng, 14–3-3, total-tau (t-tau), neurofilament light chain (NfL), and phospho-tau181 (p-tau) in CSF samples from consecutive patients with CJD (n = 220) or non-prion rapidly progressive dementia (np-RPD) (n = 213). We evaluated and compared the diagnostic accuracy of each CSF biomarker and biomarker combination by receiver operating characteristics curve (ROC) analyses, studied SNAP-25 and Ng CSF concentrations distribution across CJD subtypes, and estimated their association with survival using multivariable Cox regression analyses. Results CSF SNAP-25 and Ng levels were higher in CJD than in np-RPD (SNAP-25: 582, 95% CI 240–1250 vs. 115, 95% CI 78–157 pg/ml, p < 0.0001; Ng: 841, 95% CI 411–1473 vs. 390, 95% CI 260–766 pg/ml, p < 0.001). SNAP-25 diagnostic accuracy (AUC 0.902, 95% CI 0.873–0.931) exceeded that of 14–3-3 (AUC 0.853, 95% CI 0.816–0.889), t-tau (AUC 0.878, 95% CI 0.845–0.901), and the t-tau/p-tau ratio (AUC 0.884, 95% CI 0.851–0.916). In contrast, Ng performed worse (AUC 0.697, 95% CI 0.626–0.767) than all other surrogate biomarkers, except for NfL (AUC 0.649, 95% CI 0.593–0.705). SNAP-25 maintained a relatively high diagnostic value even for atypical CJD subtypes (AUC 0.792, 95% CI 0.729–0.854). In Cox regression analyses, SNAP-25 levels were significantly associated with survival in CJD (hazard ratio [HR] 1.71 95% CI 1.40–2.09). Conversely, Ng was associated with survival only in the most rapidly progressive CJD subtypes (sCJD MM(V)1 and gCJD M1) (HR 1.81 95% CI 1.21–2.93). Conclusions In the clinical setting, CSF SNAP-25 is a viable alternative to t-tau, 14–3-3, and the t-tau/p-tau ratio in discriminating the CJD subtypes from other RPDs. Additionally, SNAP-25 and, to a lesser extent, Ng predict survival in CJD, showing prognostic power in the range of CSF t-tau/14–3-3 and NfL, respectively. Ausführliche Beschreibung

Autor*in:	Bentivenga, Giuseppe Mario [verfasserIn] Baiardi, Simone Mastrangelo, Andrea Zenesini, Corrado Mammana, Angela Polischi, Barbara Capellari, Sabina Parchi, Piero

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	Cognitive Disorders Dementia Prion disease SNAP-25 Neurogranin Tau Neurofilament Synapses Creutzfeldt-Jakob

Anmerkung:	© The Author(s) 2023

Übergeordnetes Werk:	Enthalten in: Alzheimer's research & therapy - London : BioMed Central, 2009, 15(2023), 1 vom: 08. Sept.
Übergeordnetes Werk:	volume:15 ; year:2023 ; number:1 ; day:08 ; month:09

Links:	Volltext

DOI / URN:	10.1186/s13195-023-01300-y

Katalog-ID:	SPR053025512