Creutzfeldt-Jakob disease is rapidly progressive and universally fatal. Prognostic biomarkers are crucial for both drug development and patient management in neurodegenerative diseases. 

We prospectively enrolled patients diagnosed with probable sCJD by the 2017 EU criteria from hospitals across Thailand from March 2023 to September 2025 through the Thai National Prion Disease Surveillance Program. Baseline CSF levels of 14-3-3 gamma (CircuLex), total tau (EUROIMMUN), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) (Quanterix) were measured. Functional status was monitored monthly using the Medical Research Council (MRC) Prion Disease Rating Scale. Associations between baseline MRC scores and biomarker levels were examined using Spearman’s correlation, and linear mixed-effect models were used to evaluate the relationship between longitudinal MRC decline and baseline biomarkers levels (dichotomized at the 75^th percentile).

Among 40 sCJD patients enrolled, median age was 67 years (IQR 60-73 years), 50% were female, median disease duration from symptom onset to CSF collection was 56 days (IQR 38-82 days), and 85% were RT-QuIC positive. Higher levels of all investigational CSF biomarkers were significantly associated with lower MRC score at baseline (Spearman’s rho = -0.53, -0.66, -0.55, and -0.61, respectively; all p<0.05). In longitudinal analyses, only CSF 14-3-3 gamma showed a significant interaction with time (β_interaction = 0.03; p<0.05) , suggesting an association with slower functional decline.

Higher CSF biomarkers of neuronal injury were associated with worse baseline functional status in sCJD. Tau, NfL, and GFAP levels did not predict differences in the rate of decline while patients with higher 14-3-3 gamma levels showed slower disease progression, warranting further investigation.