CSF levels of SNAP-25 are increased early in Creutzfeldt-Jakob and Alzheimer's disease. Issue 10 (22nd August 2022)

• Record Type: Journal Article
• Authors: Halbgebauer, Steffen; Steinacker, Petra; Hengge, Sophie; Oeckl, Patrick; Abu Rumeileh, Samir; Anderl-Straub, Sarah; Lombardi, Jolina; Von Arnim, Christine A F; Giese, Armin; Ludolph, Albert C; Otto, Markus
• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 93:Issue 10(2022)
• Page Start: 1059
• Page End: 1065
• Publication Date: 2022-08-22
• Subjects: Creutzfeldt-Jakob disease -- Alzheimer's disease -- CSF; Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp-2021-328646
• Languages: English
• ISSNs: 0022-3050

Abstract

Abstract : Background: Synaptosomal-associated protein 25 (SNAP-25) in cerebrospinal fluid (CSF) is an emerging synaptic biomarker for the early diagnosis of Alzheimer's disease (AD). However, comprehensive studies investigating the marker in Creutzfeldt-Jakob disease (CJD) and in the differential diagnosis of neurodegenerative diseases are still lacking. Methods: We developed a novel, sensitive ELISA for the measurement of SNAP-25 in CSF. In total, we analysed 316 patients from 6 diagnostic groups comprising patients with AD (n=96), CJD (n=55), Parkinson's disease spectrum (n=41), frontotemporal lobar degeneration (n=25) and amyotrophic lateral sclerosis (n=24) and non-neurodegenerative control patients (n=75). Using receiver operating characteristic curve analysis, we analysed the differential diagnostic potential and compared the results with core AD biomarkers. Results: SNAP-25 CSF concentrations were elevated in AD and CJD (p<0.0001) but not in the other neurodegenerative diseases. Increased levels were observed already at early AD and CJD stages (p<0.0001). In CJD, SNAP-25 levels correlated negatively with survival time (r=−0.33 (95% CI −0.57 to −0.04, p=0.02). For the discrimination of AD from all other diseases except CJD, we observed a good diagnostic performance for CSF SNAP-25 (area under the curve (AUC) 0.85) which was further improved by applying the ratio with CSF amyloid-β 1–42 (AUC 0.95). For CJD, we could demonstrate a strong differential diagnostic potential against all other groups including AD (AUC 0.97). Conclusion: Using the novel established CSF SNAP-25 ELISA, we here demonstrate the applicability of SNAP-25 as an early synaptic biomarker for both AD and CJD with a possible prognostic value in patients with CJD.