A developing synaptic biomarker for the early diagnosis of Alzheimer’s disease (AD) is synaptosomal-associated protein 25 (SNAP-25) in cerebrospinal fluid (CSF) (AD). However, there is a lack of extensive research on the marker’s role in Creutzfeldt-Jakob disease (CJD) and the differential diagnosis of neurodegenerative diseases. To assess SNAP-25 levels in cerebrospinal fluid, researchers created a unique, highly sensitive ELISA. They analysed data from 316 people with 6 different diagnoses: Alzheimer’s disease (n=96), Creutzfeldt-Jakob disease (n=55), Parkinson’s disease spectrum (n=41), frontotemporal lobar degeneration (n=25), amyotrophic lateral sclerosis (n=24), and non-neurodegenerative control individuals (n=75). Researchers evaluated the differential diagnostic potential using receiver operating characteristic curve analysis and compared the findings to established AD biomarkers. The concentration of SNAP-25 in cerebrospinal fluid (CSF) was significantly higher in Alzheimer’s disease and Creutzfeldt-Jakob disease (P<0.0001) than in other neurodegenerative disorders. Early stages of Alzheimer’s disease and Creutzfeldt–Jakob disease showed significantly elevated levels (P<0.0001). There was a negative relationship between SNAP-25 and overall survival in CJD (r=−0.33; 95% CI, 0.57 to 0.04; P=0.02). CSF SNAP-25 had a high area under the curve (AUC) of 0.85 for separating AD from all other disorders except CJD, and its diagnostic effectiveness was further enhanced by using the ratio with CSF amyloid-β 1-42. (AUC 0.95). Researchers could show that CJD had high diagnostic potential compared to all other categories, including AD (AUC 0.97). In this study, they used the recently developed CSF SNAP-25 ELISA to show that SNAP-25 can be used as an early synaptic biomarker for both AD and CJD, and that it may have predictive significance in CJD patients.

Source: jnnp.bmj.com/content/early/2022/08/22/jnnp-2021-328646